Chemo Disturbs Sleep in Breast Cancer Patients

Patients treated with chemotherapy have disturbed sleep-wake activity, a prospective study from Hong Kong and Australia confirms.

“The first administration of adjuvant chemotherapy is associated with sleep disturbance and sleep-wake activity rhythm disruption among breast cancer patients, while the disturbance and disruption during the last cycle are less severe,” the researchers write in Sleep, online December 14.

“Nevertheless, repeated administration of chemotherapy results in progressive impairment of nocturnal melatonin production,” they add.

Dr. Lap Ah Tse of the Jockey Club School of Public Health and Primary Care of the Chinese University of Hong Kong and colleagues investigated the patterns of sleep, sleep-wake activity rhythm, and first morning void urinary melatonin levels in 180 patients undergoing adjuvant chemotherapy for stage I-III primary breast cancer.

At baseline, the median participant age was 53, and most were married with high school or higher education; 76% reported sleep disturbance (Pittsburgh Sleep Quality Index (PSQI) 5 or higher); 85% had good performance status; and 72% had undergone mastectomy.

Guided by their disease condition and preference, patients received one of three adjuvant chemotherapy regimens: six cycles of FEC-T (5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel; 44% received this), four cycles of doxorubicin plus cyclophosphamide (29%), or four cycles of docetaxel plus cyclophosphamide (27%).

Participants completed a baseline questionnaire about sociodemographics and lifestyle, including age, education level, family income, marital status, and drinking history; they completed the PSQI to evaluate their subjective sleep quality; and the researchers reviewed their medical records.

The patients wore wrist actigraph monitors GENEActiv Original (Activinsights Company, UK) on the non-dominant hand for a week before chemotherapy, and during the first week of the first cycle. Afterwards, those treated with doxorubicin plus cyclophosphamide or with docetaxel plus cyclophosphamide wore the monitor during the first week of the fourth cycle (end of chemotherapy), and those on FEC-T wore the monitor during the first week of the third cycle (end of FEC). They collected their first morning void urine samples before treatment as well as during their first and the last cycle.

The actigraphy data were extracted to determine sleep efficiency, sleep duration, total nighttime wake time, percent rhythm, F-statistic, amplitude, mesor, and acrophase.

Researchers also assessed urinary 6-sulfatoxymelatonin (aMT6s) levels.

Linear mixed-effects models were used to calculate the changes in actigraphy values as well as first morning urinary aMT6s before and during chemotherapy, and univariable and multivariable models were used for all actigraphy values and urinary aMT6s. The multivariable linear mixed-effects models were adjusted for cancer stage; age; body mass index; menopausal status; performance status; surgery type; comorbidities; corticosteroid use; sociodemographics; alcohol consumption; and chemotherapy.

Compared with baseline, sleep efficiency during the first and last cycle decreased by 10% and 5%, respectively; rhythm decreased by 27% during the first cycle and 21% during the last cycle; and during the first and last cycles, aMT6s levels decreased by 11% and 15%, respectively, compared to baseline.

“This study provides the first epidemiological evidence that nocturnal melatonin secretion is progressively impaired over the course of chemotherapy in breast cancer patients receiving chemotherapy,” the authors write.

The authors note that disturbed sleep with weak sleep-wake activity rhythm is a common problem among breast cancer survivors who have chemotherapy.

“This longitudinal study suggests that sleep, sleep-wake activity rhythm, and nocturnal melatonin production are rapidly disrupted after the administration of the first cycle of adjuvant chemotherapy in breast cancer patients,” they write.

“Sleep disturbance is associated with poor quality of life, fatigue, and depression in breast cancer patients. Weak sleep-wake activity rhythm is evident to be a prognostic risk factor associated with poor survival of cancer patients and the side effects of anti-cancer treatment,” they add. “Furthermore, disruptions in sleep and sleep-wake activity rhythm may disrupt the production of nocturnal melatonin, which is an endogenous hormone playing a pivotal role in alleviating oxidative stress and regulating the immune and hematological system.”

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.

What Are the Best Yoga Poses for Breast Cancer Patients?

Breast cancer and its treatment may cause symptoms such as fatigue, nausea, decreased range of motion, and weakness. Exercise and other integrative therapies, including yoga, can ease these symptoms, help patients feel better during treatment, and can be scaled to fit each patient’s unique needs and abilities.

“Yoga has many physical and emotional benefits for all cancer patients,” says Ann Marie Turo, OTR/L, yoga instructor in Dana-Farber’s Leonard P. Zakim Center for Integrative Therapies, where she teaches chair yoga, Hatha yoga, Pilates, yogalates (yoga and Pilates fusion), and foot fitness classes. For breast cancer patients, who might experience lymphedema following surgery or radiation, Turo says yoga can help restore range of motion in the arms and improve strength and mobility. Yoga can also reduce stress and anxiety, which in turn can lower heart rate and blood pressure.

“Research has increasingly shown that breast cancer patients who practice yoga experience many benefits, including increased energy, diminished anxiety, and better overall quality of life,” says Jennifer Ligibel, MD, a breast oncologist in Dana-Farber’s Susan F. Smith Center for Women’s Cancers and director of the Zakim Center. “The mission of the Zakim Center is to provide patients access to integrative therapies with proven benefits, such as yoga, to help support healing during and after cancer treatment.

Specific benefits of regular yoga practice include increased body awareness; improved cardiovascular, respiratory, and bone health; better blood flow; and enhanced mood, sleep, and concentration, which are often compromised during treatment.

“Yoga is a feel good exercise,” adds Turo. “And it’s a tool you can use anywhere – in bed, sitting on a chair, or on a mat.”

Turo recommends easing into a yoga routine, and some of her favorite poses can be done in a chair or at a desk. View the infographic below for a step-by-step guide to stretches that will help increase range of motion and body awareness following breast cancer treatment.


Yoga for cancer patients infographic

Breast Ca Patients Need Better Cardiac Monitoring

Physician characteristics had more influence than patient factors on adequate monitoring.

 Breast cancer patients received suboptimal cardiac monitoring during treatment with trastuzumab (Herceptin), according to a large population-based study.

Among more than 2,000 patients, only 36% of evaluable participants received adequate monitoring for cardiotoxicity in accordance with current guidelines, reported Mariana Chavez-MacGregor, MD, of the MD Anderson Cancer Center in Houston, and colleagues.

Interestingly, physician characteristics had more influence than patient factors on cardiac monitoring, they wrote in the Journal of Clinical Oncology

“We suspected that the rates of cardiac monitoring were going to be low, but we were surprised on how low, particularly in this high-risk group of patients,” Chavez-MacGregor, a medical oncologist, told MedPage Today in a separate interview. “Of particular concern was that even among patients with cardiac comorbidities the rates of cardiac monitoring were not higher.”

Specifically, female sex and graduating with a medical degree after 1990 were associated with an increased likelihood of adequate cardiac monitoring. “It is possible that younger graduates are more familiar with the use of trastuzumab, its side effects, and the current guidelines,” said Chavez-MacGregor. “It was surprising, however, to see a gender difference.”

Because trastuzumab-related cardiotoxicity is reversible, efforts to improve the adequacy of cardiac monitoring are needed, particularly in a vulnerable population,” the authors wrote, adding that adequate monitoring among these patients should be considered a marker of quality of care. Disseminating current guidelines should be a priority for hospitals, training programs, and medical societies, they added.

“In terms of trends, probably the more reassuring finding is that the rates of adequate cardiac monitoring are improving with time, suggesting that, as providers, we are becoming more aware of the current guidelines and recommendations,” Chavez-MacGregor said. “But all changes in patterns of care take time.”

They used the Surveillance, Epidemiology, and End Results, the Medicare and the Texas Cancer Registry, and Medicare-linked databases, to identify 82,751 patients, ages 66 and older, diagnosed with nonmetastatic breast cancer from 2005 to 2009. The study-eligible cohort was narrowed to a much smaller cohort of 2,203 stage I-III patients with full Medicare coverage who received adjuvant trastuzumab-based chemotherapy.

According to the manufacturer’s insert, patients on trastuzumab therapy need to have baseline cardiac assessment and frequent subsequent cardiac monitoring.

Baseline cardiac evaluation was performed in 78.8% of patients, and 68.2% had a test within the first 4 months of therapy. However, subsequent monitoring — one cardiac evaluation at least every 4 months during therapy — was performed in only 42.6%. In the entire cohort, only 36% of the patients had guideline-adherent cardiac monitoring according to the definition and current guidelines. Older patients were less likely to receive adequate monitoring (P=0.001).

By multivariable analysis, factors associated with optimal monitoring included a more recent year of diagnosis. Using 2005 as a reference year, the hazards ratios were as follows:

  • 2007: HR 1.42 (95% CI 1.07-1.88)
  • 2008: HR 1.65 (95% CI 1.21-2.27)
  • 2009: HR 1.83 (95% CI 1.32-2.54)

Other predisposing factors were anthracycline use (HR 1.39, 95% CI 1.14-1.71), a female treating physician (HR 1.37, 95% CI 1.10-1.70), and a physician graduating after 1990 (HR 1.66, 95% CI 1.29-2.12).

 The presence of cardiac comorbidities was not a determinant. Of the variance in the adequacy of monitoring, 15.3% was attributable to physician factors and 5.2% to measured patient factors.

The study had limitations, including its retrospective nature, the challenges of research based on data from insurance claims, and the relatively small proportion of patients treated with adjuvant chemotherapy — an example of the undertreatment that is “a well-described phenomenon among the elderly,” they wrote.

Breast Radiotherapy Not Linked to Cardiac Conduction Problems

Women who undergo breast cancer radiotherapy do not face an increased risk for subsequent heart conduction problems requiring a pacemaker as a result of their treatment, according to new research reported here at the European Society for Radiotherapy and Oncology (ESTRO) 3rd Forum.

“If a woman receives a pacemaker after breast cancer we can assure her it was not due to her therapy,” said study investigator Jens Christian Rehammar, MD, from Odense University Hospital in Denmark.

“Our study is quite unique, as there are no corresponding large studies in breast cancer patients only — previous studies are often mixed with patients with Hodgkin’s lymphoma,” he told Medscape Medical News.
The findings are good news considering recent evidence that an increase in other types of cardiac problems is associated with breast radiotherapy, Dr Rehammar said. He was referring to a 2013 study that found that for every additional gray of radiation to the breast there is 7.4% increase in major coronary events (P < .001) including myocardial infarction, the need for coronary revascularization, and dying from ischemic heart disease ( N Engl J Med. 2013 Mar 14;368(11):987-998).

Analysis of Danish Data

Dr Rehammar’s study merged data from the Danish Breast Cancer Collaborative Group with data from the Danish Pacemaker and ICD Registry to compare women who did and did not receive breast radiotherapy and their likelihood of needing a subsequent pacemaker.

A total of 44,704 women were included in the analysis.

The study found that among 18,308 breast cancer patients who received radiotherapy, 179 (0.98%) received a pacemaker, 90 of whom had been treated for left-sided and 89 for right-sided breast cancers.

For comparison, 1.54% of the nonradiotherapy patients received a pacemaker.

After adjusting for year of treatment, age, and time since breast cancer diagnosis, the risk for cardiac conduction problems requiring a pacemaker was not significantly different between the two groups (relative risk, 1.06; P = .71), he said.
Asked by Medscape Medical News to comment on the findings, Ben Smith, MD, assistant professor of radiation oncology at The University of Texas MD Anderson Cancer Center in Houston, said, “Conduction problems have not really been studied before in breast patients, to my knowledge. I would have predicted this would be a negative study, but it is nice to have data to confirm that.”

Dr Smith, who wrote a recent review of cardiac effects of breast radiotherapy, added, “This study provides reassurance that the typical doses of radiation received by the heart during this era in Denmark did not produce clinically severe damage to the heart’s conduction system. When coupled with prior studies, this body of work suggests that the primary mechanism for cardiac damage following breast cancer radiation is vascular in origin. The conduction apparatus in the heart is fair away from the breast, whereas the blood vessels that feed the heart are closer to the breast.”