Major Trial: Partial Breast Radiation Good for Early Breast Cancer


Accelerated partial breast irradiation (PBI), although not 100% equivalent to whole-breast irradiation (WBI) for disease control in patients with early- stage breast cancer, yields outcomes so similar that it may be considered a viable treatment option for many patients, a long-term follow-up of the largest trial of its kind indicates.

“In an effort to improve quality of life for our patients, we studied whether or not we could reduce overall treatment times significantly down to a week or less by doing a technique known as partial breast irradiation, meaning limiting radiation only to the lumpectomy cavity region and accelerating treatment down to 5 days or less,” Frank Vicini, MD, MPH, Radiation Oncology Institute, Pontiac, Michigan, told a press briefing held here during the San Antonio Breast Cancer Symposium (SABCS) 2018.

“And while [we] cannot declare that WBI and PBI are equivalent in controlling local-in-breast tumor recurrence…the absolute difference in the 10-year cumulative incidence of IBTR [ipsilateral breast tumor recurrence] was only 0.7%…. So PBI may be an acceptable alternative to WBI for a proportion of women who undergo breast-conserving surgery,” he concluded.

The NRG (NSABP B-39/RTOG 0413) trial randomly assigned 4216 women who had recently undergone lumpectomy to receive either WBI or accelerated PBI. Women enrolled in the study had zero to three positive axillary nodes on study entry.

Twenty-five percent of the group had ductal carcinoma in situ (DCIS), 65% had stage I breast cancer, and 10% had stage II disease. The majority of women also had hormone receptor—positive tumors.

Women who were assigned to the WBI arm following adjuvant chemotherapy received daily treatment with 2.0 Gy/fraction of radiation totaling 50 Gy with a sequential boost to the surgical site.

Duration of WBI was 5 to 6 weeks, which was the standard of care at the time the trial was designed.

Those assigned to accelerated PBI prior to adjuvant chemotherapy received twice-daily treatment with 3.4 to 3.85 Gy given as either brachytherapy or 3D external-beam radiation.

Patients who underwent accelerated PBI received a total of 10 treatments over 5 to 10 days.

“The primary endpoint was to determine whether or not PBI results in IBTR — both DCIS and invasive breast cancer — was the same as it was for WBI,” Vicini noted.

At a median follow-up of 10.2 years, Vicini and colleagues documented a total of 161 IBTRs as first events — 90 among women treated with accelerated PBI, and 71 for those treated with WBI.

On the basis of the upper limit of the hazard ratio confidence interval, “PBI did not meet the criteria for equivalence to WBI in controlling IBTR,” Vicini reported.

On the other hand, the 10-year cumulative incidence of IBTR was very low in both groups, at 4.6% for patients in the accelerated PBI arm vs 3.9% for those in the WBI arm.

Furthermore, the difference in recurrence-free interval rates between the two arms — 91.8% in the accelerated PBI group vs 93.4% in the WBI group — was also negligible, at only 1.6%, Vicini added.

There were no differences in distant disease-free interval (DDFI), overall survival (OS), or disease-free survival (DSF).

For example, at 10 years, 96.7% of patients in the accelerated PBI arm were free of distant disease, as were 97.1% of patients in the WBI arm.

At the same follow-up point, 90.6% of patients in the accelerated PBI arm were still alive, as were 91.3% of those treated with WBI.

DSF rates were also very similar between the two treatment arms, Vicini noted.

Rates of grade 3 toxicity were similar between the two treatment groups, at 9.6% in the accelerated PBI group and 7.1% for those who received WBI. Rates of higher-grade toxicities were also very low and were similar between the two treatment groups.

Additional analyses are currently underway to evaluate secondary endpoints, including quality of life and cosmetic outcomes, Vicini noted.

“There have been many studies looking at quality of life [after radiotherapy], and you can imagine that quality of life is better with PBI — it’s pretty intuitive,” Vicini noted.

“And there is a pretty dramatic difference in the treatment interval from 5 to 7 weeks [with WBI] down to a week or less [with PBI], so as long as the control rates are the same, the trend in oncology now is ‘less is better,’ ” he added.

Furthermore, DDFI, OS, and DFS were not different between the two arms. Arguably, these endpoints are more important than recurrence, Vicini suggested, even though recurrence is an important event for patients.

“These findings suggest that the less burdensome radiation method of accelerated PBI may be an acceptable choice for many women,” Vicini said.

“So I think this is a very important study and it certainly is important to patients,” he concluded.

PBI Not Commonly Used

Asked by Medscape Medical News to comment on the findings, press briefing moderator Virginia Kaklamani, MD, University of Texas Health, San Antonio, noted that the majority of patients in the United States who are similar to those in the current study are still undergoing WBI. “PBI is not as common as it should be,” she noted.

“In the end, this is detrimental to patients, because if they have WBI, they have to come in for radiation therapy for at least 5 and sometimes 7 weeks, whereas otherwise [with PBI], they would be coming in for 5 to 10 days,” Kaklamani added.

She felt that findings from the current study “absolutely” should provide reassurance that radiation oncologists can offer accelerated PBI to patients who meet the same criteria as those included in the current study.

“We have many trials evaluating shorter radiation intervals,” Kaklamani noted.

“And the medical community needs to be implementing more PBI, and patients should also be asking for it,” she suggested.

Reshma Jagsi, MD, DPhil, professor and deputy chair, Department or Radiation Oncology, University of Michigan in Ann Arbor, felt that high-quality randomized trials such as this one in which shorter courses of accelerated PBI were compared to WBI are “critically important” to help inform treatment decisions that women who are diagnosed with breast cancer must make each year.

“These decisions depend on the patient’s own values and preferences,” Jagsi told Medscape Medical News in an email.

For example, some women might prefer to come in twice a day for a week rather than daily for many weeks to minimize disruption of their work schedule or because of problems involving transportation, whereas others might quite reasonably decide otherwise.

“The contribution of trials like these is to arm each woman with the precise risk information she needs to make the decision that is right for her,” Jagsi wrote.

“These trialists have made an enormous contribution through this work,” he concluded.

Advertisements

Ask the Expert: Breast Cancer, Diet and Exercise


Cancer Connect

CancerConnect partnered with Dana-Farber to engage with breast cancer expert, Jennifer A. Ligibel, MD, of the Susan F. Smith Center for Women’s Cancers at Dana-Farber. Dr. Ligibel guest-moderated a question-and-answer session on “Breast Cancer, Diet and Exercise.”

Dr. Ligibel has authored several papers on the role of lifestyle factors and breast cancer, including a recent study on the impact of exercise on reducing drug-related joint pain. She is also an assistant professor of medicine at Dana-Farber.

Join us in the Breast Cancer Community on CancerConnect to view the entire Ask the Expert session with Dr. Ligibel.

Question about lifestyle factors, breast cancer and depression: Are there any ‘lifestyle’ type of factors—diet/nutrition, that might help with anxiety, depression (I didn’t seem to have these issues until after my breast cancer diagnosis)?

Dr. Ligibel:There are many studies that show that exercise has a positive impact on anxiety and depression. Studies suggest that fairly modest amounts of exercise can improve mood. We generally recommend that women start slowly and check with their physicians before starting an exercise program, but research suggests that moderate physical activity, such as walking, is safe for most breast cancer survivors and can have many positive health effects.

Although information is more limited in cancer survivors, there is also evidence that weight loss can have a positive effect on depression in women.

Question about health benefits of green tea or tumeric: What do you think of the health benefits of green tea, specifically Matcha green tea? Also, what about tumeric?

Dr. Ligibel:There is a lot of interest in the health benefits of specific supplements, but not much evidence that these products have any benefits for cancer survivors. Green tea has been studied as a potential nausea-preventing intervention, but the results of these studies have been mixed. Some preliminary results from animal studies have suggested health benefits of turmeric, but it is too early to know whether either of these supplements will eventually be shown to be beneficial for cancer survivors.

It is important to note that green tea and turmeric are foods rather than medications, like most supplements. This means that they are not regulated by the FDA. Companies that produce them can make all kinds of health claims, as long as they include the statement that the claims are not supported by the FDA. This can be confusing for patients, as many of these products are marketed as “cancer-fighting”.

Question about Optimal Types of Fat: I’m a 9-year breast cancer survivor. I’ve seen studies which favor a low fat diet to reduce the risk of breast cancer and recurrence. These studies do not specify types of fat. Do they look at or compare trans fats, fat from meat, dairy and processed foods, fats from nuts, seeds, olive oil, coconut oil, etc? I am mostly vegetarian and my diet is actually fairly high in fat since my protein comes from nuts, seeds and some eggs. What is your sense about high fat vs low fat and if the types of fats consumed contribute to higher or lower risk? I’d like to believe that healthy fats are not risk factors! Thank you.

Dr. Ligibel:The study that showed that eating a low fat diet reduced the risk of breast cancer recurrence, called the Women’s Interventional Nutrition Study or “WINS”, was largely conducted in the 1990’s, when there was not as much of a focus on different types of fat. Thus there is unfortunately not a lot of evidence to provide an answer for your question about the impact of different types of fat on breast cancer recurrence rates. However, in the years since the WINS study was conducted, research in other disease such as heart disease, has shown that all fats are not equal in terms of the impact that they have on a person’s risk of developing different diseases. There is also evidence from population studies that suggest that individuals who consume healthy fats seem to be at lower risk of some kinds of cancers, although we can’t determine if there is a cause and effect relationship between the types of fats a person eats and their risk of cancer from this kind of study.

A number of on-going studies are looking at whether there is a “best” diet for breast cancer survivors, but evidence is not conclusive at this point. Some evidence suggests that keeping weight in a good range might be more important than specific dietary ingredients. The National Heart, Lung and Blood Institute, a group that prepares many of the recommendations about weight and diet for the US population, currently supports the use of a number of diets to maintain a healthy weight.

Thus there is no simple answer to your question, but if your diet is successful in keeping your weight in a good range, it is likely a reasonable plan for you to continuing following.

Question about Exercise and Health Benefits: I have a very physically demanding job where I move at a great clip outdoors for at least 3-4 hours each day. When I am done work I have no energy for formal exercise, especially since BC treatment and Tamoxifen, just stretching or a little Yoga. Is this enough?

Dr. Ligibel:Studies have shown that physical activity, no matter how it is achieved is linked to better outcomes in breast cancer. Sometimes it is hard to know how much activity a person is doing as part of a work day, so one way to make sure that you are doing enough exercise is to wear a pedometer to track the distance you walk each day as part of your job and during your leisure time. You should aim for 10,000 steps per day. If you are accomplishing this much walking during your average work day, you are likely achieving enough physical activity to provide health benefits.

Question about Weight Loss: I am taking Anastrozole. It is very difficult to lose weight. Do you have any suggestions as to offsetting the effects of this medication on weight loss? What should the majority of the diet include and what should be omitted in order to lose weight?

Dr. Ligibel:There are many reasons why woman with breast cancer gain weight or have difficulty in losing it after breast cancer diagnosis. Some women go through menopause as a result of chemotherapy or other cancer treatments. The average women who undergoes a “normal” menopausal (not due to cancer treatment) will gain 5-10 pounds in the years after her menstrual cycles stop. This weight gain can be even greater when it occurs suddenly as a result of breast cancer treatment. Many women also feel fatigued as a result of their breast cancer therapy and become less physical active. Studies have shown that weight gain is not increased in women taking tamoxifen or anastrozole, but it is harder to study the effects of these drugs on a woman’s ability to lose weight.

Regardless of the reasons for weight gain, weight loss requires calorie reduction. This can be accomplished in many ways. A diet that is low in fat and high in fruits and vegetables has been a standard for weight loss for many years, but low carbohydrate, vegetarian, low glycemic index and Mediterranean diets can also be used to lose weight. Many people find keeping a journal of what you eat and drink as a first step to understanding your eating patterns. You might be surprised by “hidden” calories you are consuming. Some people also find a structured meal plan to be helpful when starting a weight loss program. Commercial programs can also be useful to teach you how to recognize where your calories re coming from and create new eating patterns.

Question about Diet/Exercise Resources: Do you have any recommendations for books or resources that would be a good guide to helping with navigating the best things to do for nutrition/exercise after breast cancer?

Dr. Ligibel:The American Cancer Society has developed a set of diet and nutrition guidelines for cancer survivors that is available on its web site.

The American Society of Clinical Oncology has also made Obesity and Cancer one of its primary initiatives this year and will be releasing a set of materials about weight, nutrition, and diet for cancer survivors in the next few weeks. This materials will be available in print and online through the Cancer.net website.

Question about Neuropathy: Can diet or exercise help neuropathy from chemo?

Dr. Ligibel:There is not a lot of evidence that diet or exercise can help neuropathy from chemotherapy. There are studies looking at glutamine, a supplement, but this product seems to work best while an individual is receiving chemotherapy treatments. On-going studies are looking at acupuncture as a potential treatment for chemotherapy-induced neuropathy.

Question about Prevention: What should we tell our daughters, sisters, mothers, wives, girlfriends about diet/exercise to help them prevent breast cancer?

Dr. Ligibel:There is a lot of evidence that a “healthy” lifestyle—keeping your weight in a healthy range, exercising regularly, and consuming a diet that is higher in fruits and vegetables and lower in fat—could reduce the risk of developing breast and other cancers. This doesn’t mean that these behaviors are 100% effective in preventing breast cancer or that people who don’t do any of these things will necessarily develop breast cancer, but the evidence does suggest that maintaining a healthy lifestyle should be part of a cancer prevention strategy.

General nutrition and physical activity recommendations from the American Cancer Society for Cancer Prevention include the following:

1. Stay Active: perform at least 150 minutes of moderate-intensity aerobic exercise each week, such as walking at a brisk pace

2. Consume a healthy diet that is low in fat and high in fruits, vegetables and fiber

3. Maintain your weight in a healthy range and attempt weight loss if you are overweight or obese

4. Limit alcohol to no more than 1 drink per day for women and 2 drinks per day for men

Question about Immune System: My questions are three-fold: First- does boosting the immune system help prevent breast cancer? Second, Is there a diet that boosts the immune system (I am a vegetarian)? And, lastIy, I just read something about a study showing that a vegetarian diet is linked to poor health—what does this mean to me as a breast cancer survivor?

Dr. Ligibel:There is a lot that we do not know about the biology that links nutrition and exercise to breast cancer. Some scientists have hypothesized that the immune system may play a role in this connection, but there is little conclusive evidence. Similarly there is not much known about how specific foods or supplements affect the immune system, so I would not recommend a particular diet to enhance the immune system.

Finally, vegetarian diets can be very healthy, as long as they contain a good balance of essential nutrients. It can be hard to consume enough protein, for example, for individuals who maintain a vegetarian diet. As long as you ensure that you consume a balanced diet, there is no reason why a vegetarian diet would be unhealthy. If you have specific concerns regarding your diet, I would recommend meeting with an oncology nutrition specialist.

Question about Diet/Exercise to help with fatigue: I have metastatic breast cancer—been on multiple treatments for what seems like forever. I am grateful to be alive but am beginning to feel what I assume are the cumulative effects of all of my treatments. Are there any recommendations for food or exercise that might help with my fatigue?

Dr. Ligibel:There is unfortunately very little information about the role of diet and exercise in patients with advanced breast cancer. However, exercise has been shown to be an effective way to reduce fatigue in many studies performed in women with early-stage cancer undergoing chemotherapy. There have been a few small studies of moderate-intensity exercise in women with advanced cancer that suggest that exercise is safe and may have benefits. I would recommend asking your doctor about starting an exercise program. As long as he or she is supportive of this, I would recommend slowing starting to exercise. It is important to set reasonable goals, and begin slowly. If you have not been exercising at all, even just walking around the block once per day can be a good start. Build up the time that you spend exercise each week, and you will likely begin to see some benefits in terms of your energy level.

Question about Weight Loss: I was diagnosed with Stage 4 Inflammatory Breast Cancer last July at the age of 31. I am currently on maintenance treatment and need to lose about 40-50 pounds. I lost a lot of my strength during treatment and I am a pretty picker eater who hates to cook. The thought of having to lose that much weight is so overwhelming even though I know it will help to decrease recurrence. Can you tell me what 2 or 3 things (whether nutrition or exercise related or both) that I can start with?

Dr. Ligibel:It can be daunting to know where to figure out where to start when you would like to lose a lot of weight. We find that people are most successful when they start with an attainable goal. Studies have shown that smaller amount of weight loss, 5-10% of your starting body weight, can have many benefits, even if people can’t lose 50 pounds.

I would recommend that you start with keeping track of what you eat for a week. Look for “hidden” calories like soft drinks, alcoholic beverages or juices, which are high in calories and not filling. Processed foods and sweets are also very high in calories with less nutritional value. Try to limit the amount of these you consume.

Start slowly with exercise if you have not been active. Make a plan to start with walking at a moderate pace for 10-15 minutes three times per week and gradually increase to every day, and then for longer periods of time.

Joining a group program (like Weight Watchers) can also be helpful for some people, or working with a weight loss “buddy”, a person with whom you can explore low calorie recipes and exercise, works for some people.

Question about Maca: I am taking Femara for ER & PR + stage III breast cancer. Is it safe to take Maca to help manage side effects of the AI?

Dr. Ligibel:There is unfortunately no safety data for this supplement for women with breast cancer.

Question about Soy: My question concerns tamoxifen, nutrition and products that contain soy. I was diagnosed 1/19/12 with invasive ductal carcinoma PR+ ER+ HER2+ and received bilateral lumpectomies, No lymph node involvement either side, 16 taxol/herception weekly infusions, 33 radiation rounds, 4 A/C, and the year’s course of Herceptin. I have been taking tamoxifen for the last year and a half and have read conflicting information about soy products. Although my hot flashes have subsided a bit, they do keep wake me up at night. I realized that many protein rich yogurts and nutrition bars have traces of soy in them. I considered soy as a supplement initially but decided against it, since the research appeared to be “”out”” on the final word (soy mimics estrogen but does it tend to promote my type of estrogen-driven cancer?). What are your thoughts on how much soy is “”good”” or harmful in contributing to recurrence? I appreciate your opinion. ”

Dr. Ligibel:There is a lot that we do not know about the relationship between soy and estrogen-driven breast cancers. Early studies showed that high doses of soy led to breast cancer formation in lab experiments, but it is not clear whether this amount of soy was remotely similar to what a woman could consume through diet. A number of recent reports looking at diet patterns in women in Asia and the US suggested that the risk of breast cancer recurrence was not increased by soy intake. Although there are some difficulties in using this information to completely conclude that soy intake is “safe” for breast cancer survivors, most experts at this point feel fairly confident that some soy intake in the diet is unlikely to be dangerous for breast cancer survivors. This means that it is likely not necessary to be reading food labels to avoid products containing soy, but I would personally stop short of endorsing soy as a supplement for a breast cancer survivor.

Question about Foods to Avoid: Are there any specific foods we should stay away from specifically if you are positive to estrogen?

Dr. Ligibel:There is a lot of debate regarding the use of soy products in women with an estrogen-positive breast cancer (please refer to the prior question regarding soy). Other foods also contain phytoestrogens, which are plant-based substances that are similar in structure to hormonal estrogen but come from plant sources. There is not a lot of definitive evidence about the risks or benefits of any of these products in women with breast cancer, but as a general rule, the moderate amounts of most of these substances in foods are considered safe.

Therefore, I would not say that there is good evidence that any food needs to be avoided for women with breast cancer, but soy products, flax seed, and alcoholic beverages (which also increase estrogen in some situations) should be taken in moderation.

BRCA1/2 Mutations Linked with Better Outcome in Triple-negative Breast Cancer


Cancer Connect

BRCA1/2 Mutations Linked with Better Outcome in Triple-negative Breast Cancer

According to the results of a small study, approximately 20% of women with triple-negative breast cancer are carriers of a BRCA1 or BRCA2 gene mutation. Triple-negative breast cancer patients with these mutations appear to have better survival than patients without these mutations. These results were recently presented at the 2010 Breast Cancer Symposium.[1]

Some breast cancers display different characteristics that require different types of treatment. The majority of breast cancers are hormone receptor-positive, meaning that the cancer cells are stimulated to grow by exposure to the female hormones estrogen and/or progesterone. These cancers are typically treated with hormonal therapy that reduces the production of these hormones or blocks their effects.  Other cancers are referred to as HER2-positive, which means that they overexpress the human epidermal growth factor receptor 2, part of a biologic pathway that is involved in replication and growth of a cell. HER2-positive breast cancers account for approximately 25% of breast cancers and are treated with agents that target the receptor to slow growth and replication.

Triple-negative breast cancer refers to cancers that are estrogen receptor-negative, progesterone receptor-negative, and HER2-negative. Triple-negative breast cancers tend to be more aggressive than other breast cancers and have fewer treatment options. Research is ongoing to determine prognostic factors such as gene mutations that may impact prognosis and help to individualize care.

In the current study, researchers from the M. D. Anderson Cancer Center evaluated the frequency and effects of BRCA1 and BRCA2 gene mutations among 77 women with triple-negative breast cancer. Inherited mutations in these genes can be passed down through either the mother’s or the father’s side of the family and greatly increase the risk of breast and ovarian cancer.

  • 15 of the 77 patients (20%) had a BRCA1 or BRCA2 mutation.
  • Five-year relapse-free survival was 86% for patients with a BRCA mutation compared with 52% for patients without a BRCA mutation.

The researchers concluded that triple-negative breast cancer patients with BRCA mutations experienced a significantly lower recurrence rate. These findings were unexpected because previous studies had not shown a difference in survival.

Patients with triple-negative breast cancer may wish to speak with their healthcare team regarding the risks and benefits of genetic testing.

Reference:

[1] Gonzalez-Angulo M, Chen H, Timms K, et al. Incidence and outcome of BRCA mutation carriers with triple receptor-negative breast cancer (TNBC). Presented at the 2010 Breast Cancer Symposium, Washington, DC, October 1-3, 2010. Abstract 160.

Genetic Testing Misses Half of Women at Risk for Breast Cancer


Nearly half of patients with breast cancer who, on multigene panel testing, are found to have a pathogenic or likely pathogenic variant for breast cancer do not meet current National Comprehensive Cancer Network (NCCN) guidelines for genetic testing, new research shows.

In a cohort of 959 women who were either currently undergoing treatment or had previously been treated for breast cancer, 49.9% met established 2017 NCCN germline genetic testing guidelines, and 50% did not, lead author Peter Beitsch, MD, Dallas Surgical Group–TME/Breast Care Network, Texas, and colleagues report.

Of those patients who met NCCN guidelines for germline testing, 9.39% had either a pathogenic or a likely pathogenic variant; 7.9% of those who did not meet the guidelines also had a pathogenic or likely pathogenic variant. The difference between the two groups was not statistically significant, the investigators add.

“Our results indicate that nearly half of patients with breast cancer with a P/LP [pathogenic/likely pathogenic] variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines,” the investigators observe.

“We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing,” they conclude.

The study was published online December 7 in the Journal of Clinical Oncology.

However, in a related editorial, breast cancer experts argue that widespread testing would detect genetic variants of unknown significance for which there are currently no established clinical courses of action.

Study Details

For their study, Beitsch and colleagues set up a multicenter, prospective registry with the help of 20 community and academic sites, all of which were experienced in cancer genetic testing and counseling.

They focussed on 959 patients who had a history of breast cancer but had not undergone prior single-gene or multigene testing.

“All patients underwent germ line genetic testing with a multicancer panel of 80 genes,” the authors explain.

“Overall, 83 (8.65%) of 959 patients had a P/LP variant,” they write.

The investigators then considered findings from only BRCA1 and BRCA2 genetic testing.

In this subgroup analysis, positive BCRA1/2 rates were fourfold higher among those who met current NCCN germline testing guidelines, at 2.51%, compared to those who did not, at 0.63% (P = .020).

However, the authors point out that patients with a clearly identifiable personal and family history consistent with NCCN testing guidelines were likely to have already undergone genetic testing and therefore would have been excluded from the study.

In contrast, rates of variants of “uncertain significance” were virtually identical between those who met current NCCN guidelines for genetic testing and those who did not.

“Carriers of clinically actionable variants in genes other than BRCA1/2 are likely to fall outside of the current guidelines,” Beitsch and colleagues point out.

“Results of our study suggest that a strategy that simply tests all patients with a personal history of breast cancer would almost double the number of patients identified as having a clinically actionable genetic test result,” they reason.

Variants of Unknown Significance

In a related editorial, Kara Milliron, MS, and Jennifer J. Griggs, MD, MPH, both from the University of Michigan Cancer Center in Ann Arbor, argue that widespread uptake of genetic testing would increase the likelihood of identifying pathogenic variants of genes for which there are no established guidelines for reducing cancer risk.

For example, pathogenic variants in ATM are associated with an increased breast cancer risk, “but there is insufficient evidence to support risk-reducing breast surgery or bilateral salpingo-oophorectomy,” they point out.

Furthermore, more widespread testing is likely to increase detection rates of variants of unknown significance, which were common in the study by Beitsch and colleagues.

“These variants present challenges for both patients and medical providers in the management of ambiguity that arises in a patient with a malignancy and family members,” Milliron and Griggs write. This issue is particularly problematic in certain racial and ethnic groups in which such variants are both more common and more poorly characterized, they add.

Of greater concern are barriers to high-quality counseling following genetic testing.

“The shortage of genetic counselors has been well documented,” the editorialists note, and currently, “many patients receive genetic testing without seeing a genetic counselor,” they state.

Lastly, the cost of widespread testing and counseling cannot be overlooked, especially when considering expanding that testing to all patients with breast cancer.

Medicare does cover BCRA1/2 testing, and some states cover genetic testing.

“Thus, costs to patients may be prohibitive in the most vulnerable populations,” the editorialists write.

NCCN guidelines for genetic testing were published about 20 years ago and were designed to identify patients who were most likely to carry BRCA1/2 variants.

This was done to reduce the number needed to test; at that time, the cost of genetic testing was $2000 to $5000 per test.

Now, it is approximately 10 times less costly to conduct germline testing than it was when the guidelines were originally established.

Still, Milliron and Griggs calculate that the call to have all women with breast cancer undergo genetic testing would amount to about $400 million in total costs to insurance companies. They arrive at this estimate by considering the current cost of $1500 per test multiplied by the number of new breast cancer cases diagnosed each year in the United States.

Exercise Preserves CV Function in Breast Cancer Patients


SAN ANTONIO — A year-long structured exercise program initiated 3 weeks after surgery for breast cancer significantly attenuated expected declines in cardiovascular (CV) function as patients continued through treatment, a Norwegian randomized, placebo-controlled study found.

The program, which took place outdoors and incorporated aerobics, weight bearing movement, and stretching, enabled almost full recovery of CV function at 12 months.

The study was presented here during the San Antonio Breast Cancer Symposium (SABCS) 2018.

“It is striking that for all [patient] groups — whether they received chemotherapy or not — there was a really good effect of being in the physical activity program,” said lead author Inger Thune, MD, PhD, Oslo University Hospital, Norway.

“Our study supports incorporation of supervised clinical exercise programs into breast cancer treatment guidelines,” Thune told Medscape Medical News at a meeting press briefing.

“CV function during treatment is a reflection of a patient’s physical function later on in life, because [poor CV function] is a marker of susceptibility to comorbidity and to overall survivorship, so its loss can be a very important issue in daily life,” she added.

Kent Osborne, MD, of the Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, wholeheartedly agreed with the idea of patients exercising throughout treatment as much as possible.

“You’d be surprised how little activity patients get after their diagnosis, and this is partly related to their families telling them, ‘You need to rest because you are on this chemotherapy,’ ” he told reporters.

“But patients need to be as active as they can. They will tolerate chemotherapy better and have better outcomes, so we have to convince the family not to treat the patient as if they are sick,” emphasized Osborne, who moderated the press event.

Study Details

The Energy Balance and Breast Cancer Aspect (EBBA-II) trial enrolled 545 women with stage I or II breast cancer following surgical excision of their tumor.

The mean age of patients was 55 years, and the mean body mass index was approximately 25 kg/m2. More than 70% of both groups had invasive breast cancer.

Approximately 22% of both groups also had lymph node metastases, and about 70% of women in both groups underwent breast-conserving surgery.

Slightly more than half of both groups underwent chemotherapy. About half of these patients received an anthracycline-based regimen, and some 40% received a taxane.

Of both groups, 80% also underwent radiotherapy, and almost 60% were treated with some form of endocrine therapy.

Three weeks after undergoing breast cancer surgery, patients were randomly assigned either to participate in a 12-month exercise program or to receive standard care.

Patients performed aerobic exercises of moderate to high intensity; there was also a weight-bearing and stretching component to the program.

The exercise program was tailored to an individual’s maximal oxygen uptake (VO2max), as assessed prior to their undergoing surgery. VO2max is a common measure of CV fitness.

Patients exercised together twice a week for 60 minutes per session and were instructed to exercise at home for another 120 minutes a week to achieve a total of 240 minutes a week of activity.

“CV capacity was assessed before surgery, at 6 months, and again at 12 months,” Thune noted.

“And at a mean of 31 mL/kg/min, the VO2max in both groups was basically identical at baseline,” she said.

Focus on Chemo Recipients

At 6 months, “the intervention group did much better at preserving their CV function than the control group, among whom there was an 8.9% decrease in VO2max,” Thune reported.

By way of comparison, VO2max in the intervention group dropped by only 2.7% at 6 months, the investigators noted.

At 12 months, CV function among those who participated in the exercise program had rebounded to almost the same VO2max levels as prior to surgery. On the other hand, those who received standard care had a 3.8% decrease in VO2max at 12 months relative to presurgical baseline levels (P < .001).

When investigators assessed VO2 levels among 242 patients who had not undergone chemotherapy, findings were again significantly in favor of the intervention group.

After 6 months of exercise, “patients in the intervention group had a 1.6% increase in the level of their VO2max, which was maintained at 12 months of follow-up,” Thune noted.

In contrast, patients in the control group had a 2.7% decrease in VO2max at 6 months. This loss persisted to 12 months, she added.

The researchers also analyzed changes in CV function for patients who had received any kind of chemotherapy as well as those who had been treated with a taxane.

Among 295 patients who received some form of chemotherapy, exercise participants experienced a 9% decrease in VO2max at 6 months, compared with a 14.2% decrease among control patients who received standard care.

Again by 12 months, VO2max had almost rebounded to presurgical baseline levels among those who exercised, whereas for control patients, VO2max was 6.4% lower than at baseline (P < .001).

A separate analysis was conducted for 212 patients who had received a taxane as part of their chemotherapy regimen.

For these patients, treatment effects were most pronounced. There was a 17.5% drop in VO2max at 6 months among control patients and a significant, though slightly less pronounced, drop among exercise participants.

However, at 12 months, VO2max had rebounded to only about 1.4% below presurgical baseline levels among exercise participants. For the control group, there was a 7.3% decrement in VO2max (P < .05).

“It is striking that for all these groups — whether they received chemotherapy or not — there was a really good effect of being in the physical activity program,” Thune noted.

“We believe that breast cancer patients receiving chemotherapy should be offered a tailored exercise program based on pretreatment levels of physical function,” she concluded.

Major Trial: Partial Breast Radiation Good for Early Breast Cancer


SAN ANTONIO — Accelerated partial breast irradiation (PBI), although not 100% equivalent to whole-breast irradiation (WBI) for disease control in patients with early- stage breast cancer, yields outcomes so similar that it may be considered a viable treatment option for many patients, a long-term follow-up of the largest trial of its kind indicates.

“In an effort to improve quality of life for our patients, we studied whether or not we could reduce overall treatment times significantly down to a week or less by doing a technique known as partial breast irradiation, meaning limiting radiation only to the lumpectomy cavity region and accelerating treatment down to 5 days or less,” Frank Vicini, MD, MPH, Radiation Oncology Institute, Pontiac, Michigan, told a press briefing held here during the San Antonio Breast Cancer Symposium (SABCS) 2018.

“And while [we] cannot declare that WBI and PBI are equivalent in controlling local-in-breast tumor recurrence…the absolute difference in the 10-year cumulative incidence of IBTR [ipsilateral breast tumor recurrence] was only 0.7%…. So PBI may be an acceptable alternative to WBI for a proportion of women who undergo breast-conserving surgery,” he concluded.

The NRG (NSABP B-39/RTOG 0413) trial randomly assigned 4216 women who had recently undergone lumpectomy to receive either WBI or accelerated PBI. Women enrolled in the study had zero to three positive axillary nodes on study entry.

Twenty-five percent of the group had ductal carcinoma in situ (DCIS), 65% had stage I breast cancer, and 10% had stage II disease. The majority of women also had hormone receptor—positive tumors.

Women who were assigned to the WBI arm following adjuvant chemotherapy received daily treatment with 2.0 Gy/fraction of radiation totaling 50 Gy with a sequential boost to the surgical site.

Duration of WBI was 5 to 6 weeks, which was the standard of care at the time the trial was designed.

Those assigned to accelerated PBI prior to adjuvant chemotherapy received twice-daily treatment with 3.4 to 3.85 Gy given as either brachytherapy or 3D external-beam radiation.

Patients who underwent accelerated PBI received a total of 10 treatments over 5 to 10 days.

“The primary endpoint was to determine whether or not PBI results in IBTR — both DCIS and invasive breast cancer — was the same as it was for WBI,” Vicini noted.

At a median follow-up of 10.2 years, Vicini and colleagues documented a total of 161 IBTRs as first events — 90 among women treated with accelerated PBI, and 71 for those treated with WBI.

On the basis of the upper limit of the hazard ratio confidence interval, “PBI did not meet the criteria for equivalence to WBI in controlling IBTR,” Vicini reported.

On the other hand, the 10-year cumulative incidence of IBTR was very low in both groups, at 4.6% for patients in the accelerated PBI arm vs 3.9% for those in the WBI arm.

Furthermore, the difference in recurrence-free interval rates between the two arms — 91.8% in the accelerated PBI group vs 93.4% in the WBI group — was also negligible, at only 1.6%, Vicini added.

There were no differences in distant disease-free interval (DDFI), overall survival (OS), or disease-free survival (DSF).

For example, at 10 years, 96.7% of patients in the accelerated PBI arm were free of distant disease, as were 97.1% of patients in the WBI arm.

At the same follow-up point, 90.6% of patients in the accelerated PBI arm were still alive, as were 91.3% of those treated with WBI.

DSF rates were also very similar between the two treatment arms, Vicini noted.

Rates of grade 3 toxicity were similar between the two treatment groups, at 9.6% in the accelerated PBI group and 7.1% for those who received WBI. Rates of higher-grade toxicities were also very low and were similar between the two treatment groups.

Additional analyses are currently underway to evaluate secondary endpoints, including quality of life and cosmetic outcomes, Vicini noted.

“There have been many studies looking at quality of life [after radiotherapy], and you can imagine that quality of life is better with PBI — it’s pretty intuitive,” Vicini noted.

“And there is a pretty dramatic difference in the treatment interval from 5 to 7 weeks [with WBI] down to a week or less [with PBI], so as long as the control rates are the same, the trend in oncology now is ‘less is better,’ ” he added.

Furthermore, DDFI, OS, and DFS were not different between the two arms. Arguably, these endpoints are more important than recurrence, Vicini suggested, even though recurrence is an important event for patients.

“These findings suggest that the less burdensome radiation method of accelerated PBI may be an acceptable choice for many women,” Vicini said.

“So I think this is a very important study and it certainly is important to patients,” he concluded.

PBI Not Commonly Used

Asked by Medscape Medical News to comment on the findings, press briefing moderator Virginia Kaklamani, MD, University of Texas Health, San Antonio, noted that the majority of patients in the United States who are similar to those in the current study are still undergoing WBI. “PBI is not as common as it should be,” she noted.

“In the end, this is detrimental to patients, because if they have WBI, they have to come in for radiation therapy for at least 5 and sometimes 7 weeks, whereas otherwise [with PBI], they would be coming in for 5 to 10 days,” Kaklamani added.

She felt that findings from the current study “absolutely” should provide reassurance that radiation oncologists can offer accelerated PBI to patients who meet the same criteria as those included in the current study.

“We have many trials evaluating shorter radiation intervals,” Kaklamani noted.

“And the medical community needs to be implementing more PBI, and patients should also be asking for it,” she suggested.

Reshma Jagsi, MD, DPhil, professor and deputy chair, Department or Radiation Oncology, University of Michigan in Ann Arbor, felt that high-quality randomized trials such as this one in which shorter courses of accelerated PBI were compared to WBI are “critically important” to help inform treatment decisions that women who are diagnosed with breast cancer must make each year.

“These decisions depend on the patient’s own values and preferences,” Jagsi told Medscape Medical News in an email.

For example, some women might prefer to come in twice a day for a week rather than daily for many weeks to minimize disruption of their work schedule or because of problems involving transportation, whereas others might quite reasonably decide otherwise.

“The contribution of trials like these is to arm each woman with the precise risk information she needs to make the decision that is right for her,” Jagsi wrote.

“These trialists have made an enormous contribution through this work,” he concluded.

New Toxicity Tool: One Oncologist’s Dream, Realized


A new tool for specifically assessing the risk of toxicity in older, early-stage breast cancer patients who are candidates for chemotherapy performs significantly better than an earlier iteration of the tool for a range of solid tumors and better than the widely used Karnofsky Performance Status method, new research indicates.

“This tool could be considered as a part of adjuvant treatment decision-making,” concluded study presenter Allison Magnuson, DO, of the James Wilmot Cancer Center, University of Rochester in New York.

The tool’s primary purpose is not to reduce or forgo chemotherapy in breast cancer patients, she said, but to illuminate domains associated with impairment, allowing targeted supportive care and helping patients “get through the treatment they need.”

She spoke here during an oral presentation at the San Antonio Breast Cancer Symposium (SABCS) 2018.

Magnuson was the second author of the study, but took the place of admired and respected first author Arti Hurria, MD, of the City of Hope Comprehensive Cancer Center in Duarte, California, who died last month in an automobile accident.

The new study “truly exemplifies [Hurria’s] passion for improving our knowledge about caring for older adults with cancer,” said Magnuson, holding back tears and her voice quivering.

The new breast cancer tool, known as the Cancer and Aging Research Group-Breast Cancer (CARG-BC), is in keeping with lead author Hurria’s articulated vision for geriatric oncology, which she had once described at an event at her home institution.

“The dream” and her mission, said Hurria, was “that all older adults with cancer will receive personalized, tailored care, utilizing evidence-based medicine with a multidisciplinary approach.”

Magnuson explained how CARG-BC offers such an approach. There a lot of tools in breast cancer to evaluate the benefits of treatment, she said. But older adults also need their toxicities/risks gauged. There are “few” tools available to assess both risks and benefits of adjuvant treatment in these older patients, Magnuson noted, and yet they are at increased risk of toxicities compared to younger, fitter patients.

Meghan Karuturi, MD, of the University of Texas MD Anderson Cancer Center in Houston, agreed: “Our ability to predict side effects in older breast cancer patients is very limited.”

Karuturi, who was not involved with the study, spoke with Medscape Medical News at the San Antonio meeting and said the field of geriatric oncology is “very enthusiastic” about the results and called the new study “a major contribution in the field.”

Karuturi said that these breast cancer patients are “generally going to do great.” Oncologists don’t want to undertreat but they don’t want to debilitate patients, either, she said.

She added that geriatric oncology greatly misses Hurria: “The impact this woman made is astounding.”

The CARG-BC presentation in San Antonio is a “beautiful story,” Karuturi said, “because one her mentees [Magnuson] is presenting her final work.”

Study Details

In order to develop the new predictive tool, the team enrolled 473 stage I to stage III patients with a median age of 70 years scheduled to receive standard chemotherapy regimens at 16 US institutions: 283 patients in a development cohort and 190 in a validation cohort.

The enrolling physicians assessed their patients before and after chemotherapy. “Treatment toxicity was common,” said Magnuson, with 46% of all patients having grade 3 to 5 toxicities. Also, among other measures, 24% discontinued treatment and 23% were hospitalized.

Next, in the data-crunching phase of the study, the authors first evaluated patients with the original CARG tool, which was intended for patients with various solid tumors, and found the older tool was significantly associated with grade 3 to 5 toxicities, with an area under the curve [AUC] of 0.64 (95% confidence interval [CI], 0.57-0.70).

They then added breast cancer tumor and geriatric assessment variables to the older model. For grade 3 to 5 toxicities, this new CARG-BC tool had an improved AUC of 0.76 (95% CI, 0.70-0.82).

The CARG-BC score ranged from 0 to 19, (low risk 0-5, middle risk 6-9, high risk 10+) and was significantly associated with grade 3 to 5 toxicities (P < .001) but, comparatively, the Karnofsky Performance Status was not (AUC 0.53; 95% CI, 0.48-0.59; P = .21).

The external validation AUC was not statistically different from the development AUC, the authors report in their abstract.

A higher CARG-BC score was associated with dose delay, dose reduction, hospitalization, and relative dose intensity (RDI) <85% (all P-value < .001).

The team also reports that 79% of patients who had a high, pretreatment CARG-BC score went on to have grade 3 to 5 toxicities vs 45% of those with a medium score and 21% of those with a low score (P < .001)

“We have developed and validated a chemotherapy toxicity risk score (CARG-BC) that predicts toxicity in older adults with stage I-III breast cancer,” summarized Magnuson.

Prophylaxis May Cut Cardiotoxicity Risk in HER+ Breast Cancer


Clear benefit for anthracycline treatment, not trastuzumab

SAN ANTONIO — The frequency of cardiotoxicity declined significantly with prophylactic antihypertensive medication for patients with early HER2-positive breast cancer treated with anthracycline-containing chemotherapy, but not trastuzumab (Herceptin), a randomized trial showed.

Although the trial did not meet the primary endpoint of cardiotoxicity in all treated patients, the incidence decreased by about half in patients who received anthracycline-containing adjuvant or neoadjuvant therapy and cardiovascular prophylaxis with a beta-blocker or angiotensin converting enzyme (ACE) inhibitor. Patients who received trastuzumab (Herceptin) without an anthracycline had a similar rate of cardiotoxicity whether they received one of the antihypertensive drugs or placebo, reported Pamela M. Munster, MD, of the University of California San Francisco, and colleagues.

“Our primary endpoint was similar for all cohorts,” Munster said at the San Antonio Breast Cancer Symposium (SABCS). “However, cardiotoxicity-free survival [CFS versus placebo] is comparable, with a hazard ratio of 0.71 for carvedilol and 0.74 for lisinopril, with a nonsignificant P-value.”

“Cardiotoxicity-free survival was longer with carvedilol or lisinopril than with placebo in patients who received anthracycline-containing regimens, but no differences were seen with the non-anthracycline regimens,” she added. “In patients with HER2-positive breast cancer treated with trastuzumab and anthracyclines, the addition of lisinopril or carvedilol should be considered.”

Two separate studies presented at the 2018 American College of Cardiology meeting in Orlando reported that cardiotoxicity from breast cancer drugs was about half as likely with prophylactic use of heart drugs in higher-risk patients, as well as an early trend for less cardiac damage.

‘Nice,’ but Not Enough?

The results are “very nice” but did not address the key issue for patients with breast cancer treated with anthracyclines and/or trastuzumab, said Steven Vogl, MD, a medical oncologist who practices in the Bronx in New York City.

“You’ve shown that you have fewer decreases in [left ventricular ejection fraction, LVEF], so you can give more trastuzumab, but did these interventions prevent dyspnea, heart failure — something that bothered the patient?” Vogl asked.

Acknowledging that his point was well taken, Munster said investigators struggled over the selection of the primary endpoint and ultimately decided that LVEF was more practical to assess than “subjective symptoms” in a community-based clinical trial involving 127 practices across the U.S.

“We will now analyze, do we in the long term actually have symptomatic changes, or is it just left ventricular ejection fraction?” she added.

Vogl continued, “There is considerable controversy about whether longer trastuzumab is better than shorter, but the bulk of the data suggest, at least for patients with the worse prognosis — positive nodes or bigger tumors — longer is better. In that situation, if that’s correct, then it’s good to give these [cardiovascular drugs] because then you get to give longer trastuzumab, regardless of whether they prevent symptoms or severe congestive heart failure — if you’re going to do the echocardiograms.”

Background and Results

Adjuvant trastuzumab remains standard of care for patients with early-stage HER2-positive breast cancer. The drug’s potential for cardiotoxicity requires monitoring and often leads to dose interruption and/or discontinuation, Munster noted. Results of several small studies suggested that treatment-induced cardiotoxicity might be prevented by prophylaxis with an ACE inhibitor or beta blocker, which are widely used to treat hypertension and heart failure.

Designing a randomized, multicenter, community-based trial of cardiovascular prevention posed several challenges, she continued. Reports about the frequency and severity of cardiotoxicity with HER2-targeted regimens varied widely. Evolving changes in practice pattern preferences for adjuvant neoadjuvant regimens have led to variation by geography and practice setting. Selection of regimens might be influenced by perceived or actual cardiac risk factors of patients with HER2-positive tumors.

Ultimately, investigators designed a randomized, double-blind, placebo controlled community-based trial involving patients with early HER2-positive breast cancer treated with trastuzumab. The design included stratification by use of anthracycline-containing chemotherapy. Patients were randomized to lisinopril (Zestril), carvedilol (Coreg and Coreg CR), or placebo, beginning day 1 of trastuzumab treatment and continuing for 52 weeks.

The trial had a primary endpoint of cardiotoxicity, defined as an absolute 10% decrease in LVEF from baseline or a 5% absolute decrease if LVEF fell below 50%. Eligible patients had early HER2-positive breast cancer and planned treatment with trastuzumab for 1 year, adjuvant or neoadjuvant cytotoxic therapy, LVEF ≥50, systolic blood pressure ≥90 mm Hg, and pulse ≥60 bpm.

Investigators randomized 468 patients 1:1:1 to placebo, lisinopril 10 mg, or carvedilol 10 mg. A total of 193 patients discontinued treatment before 52 weeks, including 86 patients who had a decrease in cardiac function. The patients remained in follow-up and 181 were eligible for efficacy analysis. Munster said 189 of 468 patients received anthracycline-containing chemotherapy in addition to trastuzumab.

The primary analysis showed similar rates of cardiotoxicity for the three treatment arms: 32% for placebo, 29% for carvedilol, and 30% for lisinopril. The carvedilol and lisinopril groups had nonsignificant trends toward better CFS, but neither difference achieved statistical significance:

  • Carvedilol: HR 0.71 (95% CI 0.47-1.07, P=0.052)
  • Lisinopril: HR 0.74 (95% CI 0.48-1.12, P=0.076)

The prespecified analysis by anthracycline use showed significant advantages for treatment with either cardiovascular agent versus placebo. Patients who received anthracycline-containing chemotherapy in addition to trastuzumab had a 51% reduction in the CFS hazard with carvedilol (95% CI 0.27-0.89, P=0.009) and a 47% reduction with lisinopril (95% CI 0.30-0.94, P=0.015). Cardiovascular prophylaxis did not affect CFS in the patients who received trastuzumab without an anthracycline.

Interruption of trastuzumab therapy occurred significantly more often in the placebo group (26.3% vs 15.4% with carvedilol and 17.3% with lisinopril, P=0.01). Anthracycline use accounted for most of the difference, as trastuzumab interruption occurred in 40.3% of the placebo group versus 19.7% of the carvedilol group and 23.0% of the lisinopril group.

Adverse events associated with carvedilol and lisinopril were consistent with their known safety profiles. Fatigue, dizziness, headache, cough, and hypertension were more common with lisinopril than with carvedilol.

SABCS session moderator Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology in Milan, called the findings “provocative and potentially practice changing.”

Studies Clarify Role of Extended AI in Breast Ca


Treatment to 10 years and beyond beneficial for some patients

Extending adjuvant endocrine therapy with an aromatase inhibitor to 10 years led to significant improvement in disease-free survival (DFS) and distant (DDFS) in postmenopausal women with hormone receptor-positive (HR-positive) breast cancer, Japanese investigators reported here.

Patients randomized to receive an additional 5 years of endocrine therapy had a DFS of 91.9% at 5 years post-randomization as compared with 84.4% among patients who stopped endocrine treatment after 5 years. However, the improved DFS did not translate into an improvement in overall survival (OS).

On the basis of the trial results, “I would recommend that patients with node-positive disease continue an aromatase inhibitor for 10 years,” said Shoichiro Ohtani, MD, PhD, of Hiroshima Citizens Hospital, at the San Antonio Breast Cancer Symposium (SABCS).

In a separate SABCS study, investigators in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) performed a meta-analysis of 11 randomized trials of extended AI treatment after prior endocrine therapy. The results showed that the benefits of extended therapy differed according to type or prior therapy, with a larger reduction in the risk of recurrence when the AI was preceded by tamoxifen.

Single AI

Upfront AI therapy for 2 to 3 years after tamoxifen is a standard approach to treatment for postmenopausal HR-positive breast cancer. Extended endocrine therapy can reduce the risk of late recurrence, said Ohtani. Data from several recent trials showed that extended AI therapy reduced the risk of secondary breast cancer, but had only a modest impact on DDFS.

Previous studies evaluating extended AI therapy involved various drugs in the category. Ohtani reported findings from the randomized AERAS trial, which specifically evaluated anastrozole (Arimidex) for extended treatment. The trial involved postmenopausal women with primary HR-positive breast cancer treated with anastrozole or tamoxifen plus anastrozole for ≥2 years, for a total of 5 years.

Patients who had completed 5 years of endocrine therapy were randomized to no additional therapy or to an additional 5 years of anastrozole. Ohtani reported findings from a median follow-up of 4.9 years for the extended-treatment phase. The primary endpoint was DFS, and secondary endpoints included DDFS, OS, and safety.

Data analysis included 1,683 patients who had a median age of 64 and BMI 23. About 95% of the patients had stage T1 or T2 disease, and about 80% had N0 nodal status ( about 98% N0-1). About 40% of the patients had received adjuvant chemotherapy, and 91% of the patients had received 5 years of anastrozole before entering the extended-treatment study. Ohtani said 75% of the patients who stopped treatment completed the trial compared with 70.1% of patients randomized to an additional 5 years of anastrozole.

The results showed a total of 117 local recurrences, including 47 local recurrences, 15 in the anastrozole arm and 32 in the patients who stopped endocrine treatment at 5 years. The additional 5 years of AI therapy was associated with a 45% reduction in the DFS hazard (P=0.0004). An extensive subgroup analysis did not identify any group of patients who did not benefit from extended endocrine therapy.

Ohtani said 70 patients developed distant metastases, 23 in the extended-AI arm and 47 in the control group. The difference represented a 49% reduction in the hazard ratio for DDFS (P=0.0077). Only seven patients died during follow-up in the extended-treatment study — four in the anastrozole arm and three in the group that did not continue therapy.

Patients allocated to anastrozole had higher rates of adverse events, including bone fractures (2.8% vs 1.1%), osteoporosis (33% vs 28%), arthralgia (19.2% vs 11.7%), joint stiffness (11.7% vs 4.9%), and hot flashes (6.7% vs 3.1%). Grade ≥3 adverse events were uncommon (<1% for each of the predefined adverse events of interest).

Meta-Analysis

The EBCTCG meta-analysis involved a total of 22,192: 7,500 treated for 5 years with tamoxifen; 12,300 treated for 5 to 10 years with tamoxifen followed by an AI; and 4,800 who received only an AI for 5 years. Median follow-up in the trial ranged between 4.9 and 6.5 years, said Richard Gray, of the University of Oxford in England.

The overall analysis showed that extended endocrine therapy with an AI led to a 24% reduction in the risk of any recurrence (9.5% vs 7.0%, 95% CI 0.70-0.83, P<0.00001); a 15% reduction in the risk of distant recurrence (6.1% vs 5.1%, 95% CI 0.77-0.95, P=0.004); and a nonsignificant reduction in breast cancer mortality (3.1% vs 2.8%, P=0.09).

Trials that evaluated anastrozole after 5 years of tamoxifen showed a significant reduction in any recurrence (10.7% vs 7.1%, relative risk 0.67, 95% CI 0.57-0.77, P<0.00001); distant recurrence (6.7% vs 5.2%, RR 0.77, 95% CI 0.63-0.93, P=0.008); and breast cancer mortality (3.5% vs 2.7%, RR 0.77, 95% CI 0.59-1.00, P=0.05).

The trials of extended AI treatment after 5-10 years of tamoxifen-AI therapy collectively showed a reduction in any recurrence (9.2% vs 7.1%, RR 0.82, 95% CI 0.73-0.93, P=0.002), but not distant recurrence (6.2% vs 5.3%) or breast cancer mortality (3.1% vs 2.9%).

The trials of extended AI treatment after 5 years of initial AI treatment also showed a reduction in the risk of any recurrence (7.9% vs 6.6%, RR 0.76, 95% CI 0.61-0.95, P=0.02, but not distant recurrence (4.7% vs 4.4%) or breast cancer mortality (2.7% vs 2.4%).

Gray said that the impact of extended AI therapy on recurrence risk depends on the type of prior endocrine therapy. Among women with prior tamoxifen treatment, extended AI therapy resulted in a larger risk reduction (RR 0.67, 95% CI 0.57-0.79, P<0.00001) as compared with women who received an AI for at least part of their initial endocrine therapy (RR 0.81, 95% CI 0.73-0.90, P=0.00010).

Dramatically reduce your breast cancer risk by simply eating more cruciferous vegetables


Image: Dramatically reduce your breast cancer risk by simply eating more cruciferous vegetables

The odds of a woman developing breast cancer are downright frightening, with one out of every eight women expected to develop invasive breast cancer at some time in her life. Although there’s no way to guarantee you won’t be one of them, there are quite a few things you can do to stack the odds in your favor.

As the second leading cause of death in the U.S., cancer has been the subject of a lot of research. One thing that scientists have consistently found to reduce a person’s chances of developing breast cancer is consuming cruciferous vegetables. Epidemiological studies have found that women who eat cruciferous vegetables each day can reduce their breast cancer risk by as much as 50 percent.

Experts believe that cruciferous vegetables have this effect because they are high in an organosulfate compound known as sulforaphane. Studies have shown that sulforaphane can not only lower your risk of getting cancer and reduce the inflammation that can trigger the disease, but it also kills cancer cells outright. This overachieving compound can also prevent the DNA changes that lead to cancer and deactivate enzymes that transform pro-carcinogens into active carcinogens.

A 2007 Johns Hopkins University study found that sulforaphane inhibits the growth of four different types of breast cancer cells. It’s not just women who can benefit; it has also been shown in studies to significantly slow the development of prostate cancer in men. For example, one study showed that consuming just 60 milligrams of sulforaphane per day in the form of broccoli sprouts was enough to slow the doubling rate of prostate cancer by 86 percent.

In addition to reducing breast cancer and prostate cancer risk, studies haves demonstrated that sulforaphane supports gut health, helping people to maintain a healthy digestive system. It can also help enhance your body’s natural detox process, and it has even been shown to reduce muscle pain after exercise. Another study found that it helps prevent the type of oxidative damage seen in the body that leads to immune system decline as people age.

The best way to get sulforaphane

If you’d like to get these benefits for yourself, there are lots of cruciferous vegetables to choose from, including broccoli, cabbage, kale, mustard greens, Broccoli sprouts, bok choy, and watercress. It’s easy to incorporate these vegetables into your diet, and there are enough different options that you won’t have to worry about getting tired of eating the same thing all the time.

However, if you want to get the most bang for your buck, experts say you should turn to broccoli sprouts. Just 140 grams of the raw sprouts are enough to give you the amounts of sulforaphane seen in many of these studies. If you can’t find organic broccoli sprouts in your local farmer’s market or grocery store, you can make them yourself easily with broccoli sprouting seeds and a glass jar.

Although it’s better to eat cruciferous vegetables raw if you’re looking for their cancer-fighting benefits, it is okay to cook them as long as you don’t overdo it. Avoid boiling them as this inactivates the enzyme that transforms the glucoraphanin in the vegetables into sulforaphane. Instead, steam them lightly for no longer than four minutes.

As more information comes to light about simple dietary changes that can reduce our risk of disease, one can only hope that breast cancer will be far less common in the future than it is now. Consuming the foods that lower your cancer risk should be part of an overall healthy diet and lifestyle, but it’s safe to say that eating cruciferous vegetables requires such a small effort for such a great potential reward.

Sources for this article include:

NaturalHealth365.com

NaturalNews.com