The San Antonio Breast Cancer Symposium is the largest meeting on this subject in the world, and once again promises to have breaking news for clinicians who treat this disease. Medscape Medical News reports a few hints about what will be presented this year after interviewing all 3 of the symposium cochairs.
“The meeting is being held here for the 37th consecutive year,” noted Ismail Jatoi, MD, PhD, professor and chief of the division of surgical oncology and endocrine surgery at The University of Texas Health Science Center at San Antonio, which is a partner for the meeting. “It draws participants from around the world, and it offers a global forum for discussion and exchange of ideas on breast cancer research, and on the diagnosis and treatment of the disease.”
Kent Osborne, MD, from the Baylor College of Medicine in Houston, Texas, which is another partner for the meeting, noted that for the last few years there has been a focus on HER2-positive (HER2+) breast cancer, with several new targeted agents showing large benefits. But this year there is more of a focus on estrogen receptor-positive (ER+) breast cancer, he said.
This is a much larger patient population — about 75% of all breast cancers are ER+ compared with about 20% to 25% that are HER2+.
Endocrine therapy plays a big role in the treatment of ER+ breast cancer, so when resistance develops, it creates a big problem. Research into elucidating the pathways involved in the development of endocrine resistance has shown that one pathway involved is PI3 kinase (PI3K), and the hope is that inhibiting this pathway could potentially restore responsiveness to endocrine therapy.
PI3K inhibitors are a relatively new class of agents, and they are looking for a place in breast cancer, Dr Osborne commented.
The first report of a blinded, randomized clinical study evaluating a PI3K inhibitor in patients with metastatic breast cancer (Abstract S2-02) will be presented at the meeting. The PI3K inhibitor in the study is pictilisib (under development by Genentech), and it is being used in combination with fulvestrant, compared with fulvestrant alone, in patients who progressed after first-line therapy with an aromatase inhibitor (AI) in metastatic disease.
“I think this is important, as this is a first,” said Carlos Arteaga, MD, director of the breast cancer program at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. He is also current president of the American Association for Cancer Research, another of the three partners for the meeting.
“It will be interesting to see the results of this trial, Dr Osborne said.”I think the expectation is that blocking this secondary inhibitory pathway as well as the endocrine receptor will be beneficial.”
Dr Arteaga noted that about 40% of patients with ER+ breast cancer have a PI3K mutation, but it is not clear if that mutation is causally associated with the development of resistance to treatment. “So from this study we will be able to see if this approach is helpful only in women who have this mutation, or in the whole population,” he commented.
Is Ovarian Suppression Necessary?
A much anticipated presentation at the meeting concerns the remaining results from the Suppression of Ovarian Function Trial (SOFT), specifically the results from the portion of that trial that compared tamoxifen alone with tamoxifen in addition to ovarian suppression for the adjuvant treatment of young women with hormone receptor-positive breast cancer (Abstract S3-08).
These results are eagerly anticipated, as they will give context to previous results already reported from SOFT and also from the Tamoxifen and Exemestane Trial (TEXT). A joint analysis from both of these trials was presented earlier this year at the American Society of Clinical Oncology annual meeting and simultaneously published in the New England Journal of Medicine.
This joint analysis showed that when the drugs were used together with ovarian suppression, the aromatase inhibitor exemestane was significantly better than tamoxifen at reducing breast cancer recurrence.
However, at the time the results were presented, experts questioned the need for ovarian suppression — which was achieved in these premenopausal women (median age 43 years by use of triptorelin, a gonadotropin-releasing hormone (GnRH) agonist, or by oophorectomy or ovarian radiation.
“We need to figure out who really needs this because an AI plus ovarian suppression is going to have more toxicity than just tamoxifen,” said Claudine Isaacs, MD, from the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC.
Dr Isaacs, who was not involved in the studies, explained that in the United States tamoxifen alone is the adjuvant endocrine standard of care for premenopausal women. She and several other experts said at the time that they would wait to see the remaining results from SOFT — which will now be presented in San Antonio — before making up their minds about this new adjuvant treatment approach.
Dr Arteaga commented that the results from the joint analysis of SOFT and TEXT had already led to some “shift in thinking.” He has colleagues who have used the approach of exemestane and ovarian suppression in patients who were at high risk, for example with a lot of positive nodes.
But will the new data support wider use of this two-pronged approach?
A major consideration for patients during and after treatment is quality of life, and this will be reported for the two tamoxifen arms of SOFT, with and without ovarian suppression, in a related presentation (Abstract S3-08).
First Data on PD Inhibition in Breast Cancer
Novel immunotherapies that act by inhibiting the programmed death (PD) pathway have shown some very exciting results in melanoma and some other cancers, Dr Osborne commented. These immune checkpoint inhibitors are showing benefits even in difficult-to-treat tumor types.
“Now at this meeting we will be hearing the very first results with PD inhibition in breast cancer,” Dr Osborne said. They come from a Phase 1b trial with pembrolizumab (Keytruda, Merck & Co) in patients with advanced triple-negative breast cancer, some of whom had been heavily pretreated patients and had recurrent/metastatic disease (Abstract S1-09).
Another first is the Phase 3 randomized trial that compares accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation; Five-year survival results will be reported (Abstract S5-03).
There will also be a special session on radiotherapy for breast cancer in countries with limited resources. “We are seeing more and more participants from developing countries, so this will be relevant to them, but it should be of interest to everyone who uses this modality,” commented Dr Jatoi.
Long-Term Data on Chemoprevention
The meeting will also hear for the first time very long-term results from the use of tamoxifen to prevent breast cancer in women who are at high risk for the disease. Results will be presented for 16 years of follow-up (Abstract S3-07) from the International Breast Cancer Intervention Study I, which randomized over 7000 patients to tamoxifen or placebo for five years.
Much of the data to date in this field of chemoprevention has been from short-term follow-up, Dr Osborne commented, and this shows that blocking the estrogen receptor does lead to a decrease in breast cancer incidence in the short-term (5 to 7 years’ follow-up).
However, as Dr Arteaga pointed out, ER+ve breast cancer has a very long latency, and late recurrences, so “these early results cannot be seen as a final victory,” he said.
“We will have to see if this holds up over time,” Dr Osborne commented. There has been some speculation that in the short term, the estrogen blockade is actually inhibiting very small breast cancers that were already there, but could not be detected, he explained.
“So some of this short-term effect is actually suppression rather than prevention,” Dr Osborne commented. “But now with these long-term results, we will have a real idea of the prevention effect.”
These long-term data will also give a better picture of the side effects of chemoprevention, which is not widely used mainly because of concern over potential toxicity, both experts commented.
Long-term Results on Fat Reduction Diet
Another set of long-term results will be presented for a diet intervention study (Abstract S5-08), specifically the final survival analysis at a median of 15 years’ follow-up from the Women’s Intervention Nutrition Study.
This study was conducted in nearly 2500 women with early-stage breast cancer (79% ER+) who received standard care; half were randomized to the diet intervention arm of the study, which specifically targeted fat intake reduction through regular individual counseling sessions with dieticians.
After a median of five years on this low-fat eating plan, the women in this intervention arm had significantly reduced fat intake (from 29.2% to 20.3% of calories, P < .0001) and had significant weight loss (-2.7 kg, P = .005), whereas the women in the control group showed no change.
But did this lifestyle intervention improve overall survival? The answer will be revealed in a late-breaking presentation (Abstract S5-08).
Will TILs Data Inform Response?
Dr Arteaga drew attention to a new analysis of the Alliance N9831 trial that will look at correlations between the presence of stromal tumor-infiltrating lymphocytes (TILs) and the clinical outcomes with adjuvant trastuzumab (Herceptin, Genentech; Abstract S1-06).
“I think this is important because one of the concepts of how trastuzumab works is that it brings immune cells to tumor cells, and facilitates the destruction of HER-2 tumor cells by host immune cells,” he explained. If these results show a correlation between TILs and benefit from adjuvant therapy with trastuzumab, they may lead the way to “a refinement” in the use of adjuvant HER2- therapy, he suggested.
This may lead to a way of identifying which women are likely to do well on trastuzumab alone, and which women may need more potent HER2 therapy, such as trastuzumab in combination with another HER2 targeted agent (eg, lapatinib (Tykerb, GlaxoSmithKline), pertuzumab (Perjeta, Genentech), or TDM-1 ado-trastuzumab emtansine (Kadcyla, Genentech). “These are very costly drugs, and not everyone needs a combination…so these data may help us to make rational choices,” Dr Arteaga commented.
He also highlighted the BOLERO-1 study, again in HER2 breast cancer, but in patients with advanced disease who are receiving trastuzumab plus chemotherapy, plus or minus everolimus as first-line line therapy (Abstract S6-01). “There are no data on this, so I expect a large audience to come and listen to these results,” he said.
One focus for the educational sessions is triple-negative breast cancer, which is “particularly difficult to treat, because we have no targeted therapies,” commented Dr Jatoi. “At the moment, the only treatment we have to offer these patients is chemotherapy,” he said. “This is an area of research that is obviously very important…and I think it will continue to be important for some time, as more and more people around the world look for ways of better ways of treating this disease.”
Another area of intense research is hereditary breast cancer, which accounts for about 10% of the disease. “We need to learn how to better tailor treatments for women who harbor the mutations, but also how to manage women who are at increased risk of breast cancer because they have these mutations…we can offer the screening, surgery, chemoprevention,” he said.
Dr Jatoi himself will be chairing a session on contralateral prophylactic mastectomy (CPM), rates of which are increasing around the world, he said. “Women who have unilateral breast cancer are choosing to have both breasts removed…this is a perplexing trend,” he commented. It’s perplexing because the rates for contralateral breast cancer are decreasing, but the rates for CPM are increasing, and they are increasing dramatically, he said. It is not just in the United States, he noted, it has also been reported in Europe and Asia. The increase also cannot be entirely explained by increased testing for BRCA mutations (which increase the risk for breast cancer, and for which prophylactic mastectomy can be recommended). This topic will be explored in the Critical Science Forum, held from 1 PM to 2 PM, on Wednesday, December 10.