Sharon S. Lum, MD, FACSProfessor in the Department of Surgery-Division of Surgical Oncology Medical Director of the Breast Health CenterLoma Linda University HealthLoma Linda University School of Medicine

Surgery Beneficial to Some HER2+ Metastatic Breast Cancer Patients Interview with:

Sharon S. Lum, MD, FACSProfessor in the Department of Surgery-Division of Surgical Oncology Medical Director of the Breast Health CenterLoma Linda University HealthLoma Linda University School of Medicine

Dr. Lum

Sharon S. Lum, MD, FACS, Professor
Department of Surgery-Division of Surgical Oncology
Medical Director of the Breast Health Center
Loma Linda University Health
Loma Linda University School of Medicine What is the background for this study?  

Response: Anecdotally, we observed that many patients with advanced HER2+ breast cancer have had tremendous responses to the new targeted therapies and the oncologists were referring them back to surgeons for consideration of local regional therapy.

While traditionally surgeons have avoided operating on metastatic breast cancer patients due to the patient’s likelihood of dying from their metastatic disease, these HER2+ patients seemed to be doing so well that surgery might make sense. In our surgical oncology clinic, we seemed to be operating more on these patients. Since these patients seemed to be living longer, they might survive long enough for their primary tumor to become a problem for them.

However, we did not have any data to support doing surgery in these cases. Prior studies have demonstrated mixed results regarding the survival benefit from surgery for stage IV breast cancer patients, but these were completed prior to routine use of anti-HER targeted therapies, so we wanted to further examine the role of surgery in HER2+ stage IV breast cancer patients. What are the main findings? 

Response: The most important finding was that our propensity score matched survival analysis revealed that surgery was significantly associated with improved survival compared to not receiving surgery. However, it is also alarming that we found increased risk of mortality in non-Hispanic black patients compared to non-Hispanic white patients, those un- or under-insured compared to those with Medicare, and in patients in the lowest income bracket of our study compared to patients in the highest income bracket. Furthermore, there were significant differences in which patients received surgery: older patients (compared with younger), non-Hispanic black patients (compared with non-Hispanic white), those who were un- or under-insured (compared with Medicare), and those treated in academic hospitals (compared to community) were less likely to have surgery.

These results suggest disparities in health care due to race and socioeconomic factors, and further research is needed on these disparities and how they can be addressed. What should readers take away from your report?

Response: Our findings suggest that, in addition to standard HER2 targeted medications and other adjuvant therapy, if a woman has stage IV HER2+ breast cancer, surgery to remove the primary breast tumor should be considered depending on their response to targeted therapies. We hope that our results encourage patients and clinicians to consider surgical treatment in the face of HER2+ metastatic disease while weighing the risks and potential benefits. What recommendations do you have for future research as a result of this work?

Response: In future work, we would like to address some of the limitations of the current study. We would like to attempt to determine the sequence and duration of different types of treatment (chemotherapy, targeted therapy, endocrine therapy, radiation) and surgery (total or partial mastectomy, axillary surgery) as it is possible that the different combination of therapies these patients are receiving, and when they are receiving them during their treatment, may have independent effects on survival.

The main limitation of this study is that we did not have specific information on which targeted therapies were used. We assumed that if a patient was reported as receiving “immunotherapy,” which is the only variable in the NCDB that documents antibody treatment, that they received trastuzumab (Herceptin), because trastuzumab was the only FDA approved monoclonal antibody during the time period of the study 2010-2012 (except for the tail end of 2012 when pertuzumab was approved). Also, although we used propensity matching to minimize selection bias, we acknowledge that we cannot control for the ability for surgeons to operate on better candidates, or those we presume will have a better outcome (“eyeball test”). Ongoing phase 3 studies of primary site surgery in stage IV breast cancer should carefully analyze HER2 subsets and targeted therapies, as well as optimize controlling for variables that can contribute to selection bias. Is there anything else you would like to add? 

Response: It is imperative to note that although our study shows a survival benefit for receiving surgery, it was retrospective in nature. While we tried to control for selection bias with propensity matching, we know that surgeons and patients are inherently selective when choosing surgery—that is, surgeons may choose to operate on healthier patients that seem likely to live longer, and we may not have accounted for all factors linked to a better outcome. Additionally, the data set we used does not contain detailed information about which specific drug regimens were used. We made the assumption that standard chemo- and immuno- therapies included some type of HER2 targeted therapy, as this was standard of care in the era of our study (2010-2012). All authors have no conflicts of interest or disclosures.


AACR abstract and presentation:

The impact of primary tumor surgery on survival in HER2 positive stage IV breast cancer patients in the current era of targeted therapy

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Last Updated on April 8, 2019 by Marie Benz MD FAAD