SABCS (San Antonio Breast Cancer Symposium) is designed to provide state-of-the-art information on the experimental biology, etiology, prevention, diagnosis, and therapy of breast cancer and premalignant breast disease, to an international audience of academic and private physicians and researchers. Members meet annually in San Antonio. This year’s symposium was December 3rd-8th.
Debra Patt, MD MPH MBA
Executive Vice President, Policy and Strategic Initiatives, Texas Oncology
Chair, Breast Cancer, US Oncology Pathways Task Force
Director, Analytics, McKesson Specialty Health
Director of Breast Health, Division of Women’s Health, Dell Medical School
We appreciate Dr. Patt for sharing highlights from this year’s annual symposium:
“San Antonio Breast Cancer Symposium 2018, a year with much progress”
As those who know me hear me say often: It is a great time to be an oncologist. We have had a time of tremendous progress in cancer care. Akin to being an infectious disease specialist with the advent of antibiotics, we have so many new tools to fight the diseases we seek to control and eradicate. This is true of breast cancer in 2018.
In 2018 coming from the SABCS we saw much progress in cancer care: Identification of which patients require more treatment to control disease and reduce risk of recurrence and which patients need less, the development of new and novel therapies to treat cancer, and how to optimally support our patients by supporting their health and managing side effects to improve their outcome. I will highlight some of the findings from this meeting and other meetings in the year.
PROGRESS IN THERAPY
As you know, breast cancer is a compilation of many different diseases. We think of ER+ Her 2 negative, Her 2 amplified, and Triple negative disease very differently.
Her 2 amplified breast cancer
In patients with Her 2 amplified breast cancer, chemotherapy combined with her 2 targeted therapy remains important to eradicating cancer.
APT for small tumors
In Her 2 amplified disease, most patients with small (less than 2cm) cancers can safely be treated with surgery first, then followed by paclitaxel for 12 weeks and adjuvant trastuzumab, the APT regimen.
KATHERINE AND EXTENET for patients with tumors that are >2cm or involve lymph nodes
Most patients who have Her2 amplified cancers that are greater than 2cm or involve their lymph nodes should benefit from having chemotherapy and targeted therapy first “neo-adjuvant” (before surgery) to optimize their response. Among patients who have complete pathologic complete response to neoadjuvant chemotherapy in combination with her 2 targeted agents like trastuzumab (Herceptin) or trastuzumab + pertuzumab (Perjeta), they have an excellent outcome with completing therapy with trastuzumab alone after definitive surgery and radiation alone, whereas patients who do not have a pathologic response will benefit from TDM-1 (Kadcyla) for an additional 14 treatments in addition to their definitive surgery and radiation as indicated. The KATHERINE study was presented at SABCS this year that demonstrated that the strategy of segregating patients by pathologic complete response, and treating patients who are higher risk suboptimal responders with an additional 14 cycles of TDM-1 instead of trastuzumab alone could reduce their likelihood of recurrence by 11% within 5 years of follow up. This changes the standard of care among Her 2 amplified patients that do not achieve a complete response to neoadjuvant chemotherapy. In addition, the EXTENET study demonstrated that among patients that did not achieve a complete response to neoadjuvant therapy that are estrogen receptor positive and had received chemotherapy with her 2 directed therapy, neratinib when taken in the adjuvant setting could further reduce risk of recurrence by 7.5% at 5 years. It is important to note the KATHERINE study was not done in coordination with the EXTENET study, and how we combine the information to serve our patients is controversial.
Can some patients have less than a year of trastuzumab?
While at this time 12 months of her 2 directed therapy remains the standard of care, the PHARE study was presented to see if 6 months of her 2 directed therapy is adequate. While this study did not meet its endpoint of non-inferiority, it falls on the heels of several other trials that evaluated less than a year of trastuzumab. While some of these trials did meet their endpoint of non-inferiority, the trend still does favor a year of treatment. That said, no patient is exactly the same and patients who have lower risk of recurrence because of favorable features or excellent response to treatment, or patients who have medical or financial toxicity associated with prolonged treatment are unlikely to substantially increase their risk if they complete less than a year of therapy. If this is something you are considering, you should talk with your doctor.
Estrogen Receptor Positive Breast Cancer
Chemoprevention with low dose tamoxifen
Patients at risk for invasive breast cancer because they have ER+ DCIS, LCIS or atypical ductal hyperplasia can reduce their risk by about half if they take chemoprevention. The TAM01 study was presented at SABCS evaluating the efficacy of low dose tamoxifen at 5mg/day for 3 years in comparison to placebo (the usual dose of tamoxifen is 20mg/day). In this study, breast cancer risk was reduced by half. We can conclude from this that low dose tamoxifen is a safe and effective way to reduce risk among patients with ADH ER+DCIS and LCIS in comparison to placebo.
As we know estrogen drives estrogen responsive breast cancer, the role of chemotherapy in patients with low risk localized breast cancer while still sometimes necessary, is diminishing. The TAILORx trial was presented at ASCO this year showing that patients with ER+ node negative breast cancer and an intermediate oncotype score on average did not benefit from chemotherapy. While chemotherapy may take a backseat, estrogen blockade is driving outcomes. Among premenopausal women with higher risk estrogen driven cancers, we now understand the benefit of suppression of ovarian function in addition to endocrine blockade to reduce the risk of recurrence. Among all women with higher risk, we understand the benefit of increasing estrogen blockade from 5 to 10 years in the trials where this was studied improved relapse free survival by 3-4%. While suppressing ovarian function and extending estrogen blockade to 10 years has not been popular among patients, it is really important to further reduce the risk of recurrence.
While prolonged estrogen blockade will lead to complications like hot flashes, new research suggests oxybutynin (starting at 2.5mg and increasing as necessary) can be an incredibly effective way to diminish hot flashes.
We continue to have new data on the role of CDK4/6 inhibitors alone or in combination with endocrine therapy in patients with metastatic breast cancer and this year they demonstrated a survival benefit in addition to a substantial improvement in disease free interval. We continue to investigate the role of these agents in the adjuvant setting, though we think they are important, and here in Austin for the next few months will continue to enroll on the Monarch E trial evaluating the role of adjuvant abemacicilb in reducing risk among high risk ER positive breast cancer patients within a year of their diagnosis. I hope high risk ER+ breast cancer patients will talk to their doctors about this important opportunity to see if they will qualify.
Triple Negative Breast Cancer
While chemotherapy remains critical in reducing the risk of recurrence for localized breast cancer, among triple negative patients with metastatic breast cancer, new novel therapies offer a lot of hope. Among BRCA positive patients, we now have two PARP inhibitors that are FDA approved, olaparib and talazoparib (regardless of ER+/-). Immunotherapy is looking promising in patients with triple negative breast cancers with Atezolizumab being presented at two major meetings this year as having a survival benefit in combination with nab-paclitaxel in comparison to chemotherapy alone. This therapy is not yet FDA approved, and the results still require longer follow up, but it is exciting to expand the spectrum of therapy opportunities and consider how we harness the immune system and the early data In a similar vein, the early data for the antibody-drug conjugate sacituzumab-govitecan (IMMU-132) looks very promising in triple negative breast cancer targeting the trop2 protein that is expressed in >90% of triple negative breast cancers and linking it to SN-38, a topoisomerase inhibitor that is the active component of the drug irinotecan we use in other cancers. It has received a breakthrough designation from the FDA and I understand will be considered for approval in early 2019.
Molecular Profiling in Metastatic Disease
While the benefit of molecular profiling more broadly in patients with metastatic breast cancer remains controversial, it is the only way to identify some of the pathways of therapeutic intervention under investigation and mechanisms of resistance. Many of the therapies under investigation presented at SABCS are only being investigated in patients whose tumors have a particular molecular susceptibility to a given cancer. In November 2018, a novel therapy was approved larotrectinib for patients with solid tumors exhibiting NTRK gene fusions. While the chances that any advanced cancer patient harbors this genetic mutation is low (1%), the response rate to larotrectinib is 75%. I was in the small room when the abstract was first presented at ASCO in 2017 in the Developmental Therapeutics section and they showed a picture of a 14 year old girl with an eggplant sized secretory breast cancer who started the drug and her cancer had gone in to remission within a month. Again, while broad molecular profiling remains controversial among patients with metastatic breast cancer, it is useful for patients to talk to their doctors about if or when it makes sense for them and what therapies or clinical trial opportunities it may identify.
How we Manage Axillary Lymph Nodes and Radiation after Surgery -AMAROS
As a medical oncologist, I am in constant awe of how my collaborating surgeons and radiation oncologists work with us to reduce risk among the patients we serve. I had the privilege of giving a talk with Dr. Monica Morrow last week, an internationally renowned breast surgeon and quite a tour de force. She updated the group on her interpretation of the AMAROS data which now has 10 year follow up. My take from this discussion is that of course patients who have no clinically palpable lymphadenopathy or lymphadenopathy detected by ultrasound should undergo a sentinel lymph node procedure in coordination with their primary breast surgery, and that if patients have a sentinel lymph node identified as having tumor within it and meet the specified study criteria, they can talk to their surgeon and radiation oncologist about the role of avoiding further surgery in a completed axillary dissection and potentially undergo axillary radiation instead. While this is not appropriate for every patient and should always be decided in collaboration with your treating physicians, the 10 year follow up, 1.82% (11 out 681 patients) of those assigned to axillary radiotherapy had axillary recurrence, compared with 0.93% (7 out of 744 patients) of those assigned to axillary lymph node dissection and a 15% reduction in the risk of lymphedema. There was no difference in disease free survival or overall survival between the treatment arms.
Exercise and Healthy Eating During Treatment and in Survivorship
While investigation of the benefits of exercise and healthy nutrition during treatment and in survivorship are not new, there were some new findings that were presented at the meeting that reinforce their importance. The EBBAII trial was presented that demonstrated a marked improvement in cardiovascular health when patients exercised after breast surgery. The benefits were especially pronounced among patients who received chemotherapy. They recovered faster and were markedly healthier at 6 months and a year. The SUCCESS C study was also reported that demonstrated weight loss with diet and exercise interventions among women with breast cancer who received chemotherapy. Specifically, the average patient gained about a kilogram during the study period and the average patient on the intervention arm that enlisted diet and exercise lost a kilogram during the study interval. Overall this represented about a 5 pound difference between the intervention and non-intervention arm.
There is so much more to tell about the conference and the year in general, but as you can see 2018 has been a year of progress in breast cancer. I hope 2019 will bring us much much more. I know with partnership of clinicians, navigators, patients, and coordinated systems of care we will get there faster. We are working on putting together an educational session covering these topics in January 2019. Please watch for that and join us.
I have tremendous gratitude for all the BCRC does to help the patients we serve. Thank you!
Dr Patt is the Executive Vice President for policy and strategic initiatives in Texas Oncology. She is a breast cancer specialist and leads breast cancer research locally for Texas Oncology and is the director of breast health services for Dell Medical School. She is a national expert on healthcare policy and clinical informatics. Serves on the national board of the Community Oncology Alliance and the leadership of the American Society of Clinical Oncology where she chaired the clinical practice committee. She also serves as the inaugural Editor in Chief of the Journal of Clinical Oncology-Clinical Cancer Informatics.