Precision Medicine a Necessary Component in HER2+ Breast Cancer Care

Mothaffar F. Rimawi, MD

Precision medicine has become essential in delivering optimal and individualized care for patients with HER2-positive breast cancer.

Specifically, this type of approach was investigated in the NSABP B-47 trial, which aimed to determine the value of trastuzumab (Herceptin) plus standard adjuvant chemotherapy in patients with low levels of HER2 protein. This trial’s findings showed no significant efficacy, demonstrating the importance of targeting treatments for patients based on their genetic mutations, explained Mothaffar Fahed Rimawi, MD, in an interview during the 2017 San Antonio Breast Cancer Symposium (SABCS).

In the NSABP B-47 study, which was presented at the meeting, results showed that the 5-year invasive disease-free survival rate was 89.6% among the 1640 patients who received trastuzumab and 89.2% among the 1630 patients who did not (95% CI, 0.77-1.26; P = .9). Investigators said the findings were no different whether patients were subdivided by HER2 immunohistochemistry level, extent of lymph node involvement, or hormone receptor status.

OncLive: What is the importance of precision medicine in HER2-positive breast cancer?

Rimawi, associate professor, Baylor College of Medicine, medical director and director of clinical research at Baylor's Lester and Sue Smith Breast Center and the Smith Clinic/ Ben Taub Hospital, and co-leader of the breast program at Baylor's Dan L. Duncan Cancer Center, discussed the significance of precision medicine in HER2-positive breast cancer, as well as the possible role of immunotherapy for this specific population.Rimawi: [At SABCS] I discussed the research that is shedding light on HER2-positive breast cancer, including mechanisms of resistance, sensitivity, and the efforts to tailor treatments to the individual patient.

From your perspective, what was the most exciting advancement in the field of breast cancer in 2017?

I moderated 2 sessions where a panel of experts received challenging cases from the audience and provided treatment recommendations based on the latest available evidence. These contributions show the strength of this [medical] meeting, where science and clinical medicine come together to push forward patient care by utilizing the best possible care models and the best science.It is hard to pinpoint 1 thing. In my opinion, the most impressive thing about breast cancer is the incremental improvement in patient outcomes that have been ongoing year after year. Although a small increment does not sound exciting, when you add those up with different treatment modalities for years, we are seeing the mortality from breast cancer going down and women are living longer, healthier lives.

You see 3 different levels of improvements or achievements. One involves very robust meta-analyses where clinical trials from all over the world pool their data together. When that happens, there are 10,000 women treated with similar treatments and followed for 10 to 20 years. Powerful data have shown us that giving patients the treatments that we know work, such as chemotherapy for higher-risk patients and endocrine therapy for estrogen receptor (ER)-positive patients, are continuing to make a difference in the lives of women. We know that giving the chemotherapy on a more dose-dense schedule has robustly demonstrated to improve outcomes for these patients. The power of collective knowledge is one area of achievement.

The other area is the strength that we are seeing in precision medicine. Multiple trials have reported showing that we need to target the right treatment to the right person. The NSABP B-47 trial that was reported at SABCS sought to determine whether anti-HER2 therapy with trastuzumab would be beneficial to women who have lower levels of HER2 expression.

This trial would be considered negative under clinical standards but, the question was, “If they have some level of HER2 expression, would they benefit from anti-HER2 treatment?” This trial showed conclusively that it is not the case. You need to target anti-HER2 treatment to those who are HER2-positive and extending a treatment that works well for 1 group of patients to other patients may not work. That is a win for precision medicine and for the idea that it is important to tailor treatment to the patients.

Moving forward, what role will immunotherapy have in the treatment of patients with HER2-positive breast cancer?

The third area that is exciting is we are still seeing a robust flow of data from new agents that are in development. We are seeing many trials focusing on the immune system and how to best stimulate it or reprogram it to fight cancer with a lot of promise. There are many other agents for other pathways that are being explored. We need to understand the biology of the tumor and the patient, and then focus the treatment that way. Hopefully, those achievements will continue year after year.The idea of using, or reprogramming, the immune system or stimulating it to fight cancer has been a dream that many people were following. The introduction of checkpoint inhibitors in many cancers over the last few years has been making a difference for the treatment of patients with cancer.

In breast cancer, there has been a robust interest in the immune system and immuno-oncology agents. Due to the clinical unmet need in triple-negative breast cancer, there is a focus of immunotherapy there because, biologically, those tumors have a higher mutational load and are more immunogenic. There is also interest in other subsets of breast cancer like ER-positive breast cancer.

There is going to be a role for immunotherapy for HER2-positive breast cancer. There are many agents that are being studied in several settings and in combination with other agents. We will see that there is a subset of patients with breast cancer who benefit from immunotherapy. Who those patients are with HER2-positive disease is something that remains to be determined based on our understanding of the biology and the impact the treatment is making. I am optimistic that the future of immune-oncology is bright.

Fehrenbacher L, Cecchini RS, Geyer CE, et al. NSABP B-47 (NRG Oncology) phase III RCT comparing adjuvant chemotherapy ACweekly paclitaxel (WP) or TC x 6 with or without trastuzumab for 1 year in high-risk, invasive breast cancer, negative for HER2 by ISH and with IHC 1+ or 2+ (HER2-Low IBC). Presented at: SABCS; December 5-9, 2017; San Antonio, Texas.