Ms. Venne. Although the numbers aren’t nearly as large as they were in the original trials looking at the lumpectomy vs mastectomy, there are now survival data for women with BRCA1/2 mutations. With all of the caveats that Dr. Manning mentioned, even if you have an identifiable mutation, you may not necessarily need that more aggressive surgery.2 Clearly, individuals with identifiable mutations would have a higher chance of a contralateral breast cancer, a second primary, so some individuals consider a prophylactic bilateral mastectomy. But from a survival perspective, there are a fair amount of data now available that say that lumpectomy vs mastectomy should really be the conversation based on all of the information that Dr. Manning outlines rather than using primarily the mutation status.
Dr. Manning. I agree.
Dr. Aggarwal. This patient had a lumpectomy and axillary lymph node dissection. Pathology reported 1.5-cm mass, grade 3 IDC; the margins were negative. There was no skin involvement, 27 lymph nodes removed were all negative. Dr. Manning, can you please discuss the role of radiation in early stage breast cancer in patients like this case?
Dr. Manning. One of the questions that is always controversial for radiation in these early stage breast cancer cases is what do you do with the nodal irradiation? Previously, radiation oncologists based treatment plans on retrospective data, but in 2015, there were 2 major studies, 1 from Canada, and 1 from the European Organisation for Research and Treatment of Cancer (EORTC).3,4 Both studies tried to determine whether there was an advantage to doing regional nodal irradiation in early breast cancer cases. That encompassed axillary, supraclavicular, and internal mammary nodes. The studies showed that there was no survival advantage, but there was a statistically significant improvement in disease free survival and in local regional recurrence and distant mets.
Unfortunately, there are still a lot of unanswered questions, like what group potentially would benefit the most? In the MA.20 Study, some observers questioned that maybe the ER-/PR- women had the most benefit, but then, in the other study the benefit wasn’t clear.4,5 One question is which lymph node group is having the most impact? Was the benefit from radiating the supraclavicular nodes or was it from radiating the internal mammary nodes? Determining the answer is important from a technical point of view because when you radiate the internal mammary nodes, you have the potential to expose more heart and lung to radiation. You have to put all these together and make a recommendation.
Clearly, for a patient with negative nodes there is no question: You would not treat the regional nodes. However, for a patient with positive nodes you really have to individualize the approach and consider age, anatomy, tumor location, and burden of axillary disease.
I would sit down and have a discussion with this young woman to weigh the risks and the benefits. There is a slight increased risk of lymphedema in these patients, and radiation pneumonitis increases, but not significantly. A key concern is to minimize the total dose of radiation to the heart. There have been great developments in radiation oncology technology and capabilities, so the cardiac dose is now less. But when you think about a 32-year-old patient and weigh the benefit of a 2% to 3% decrease in the incidence of distant metastases and no OS advantage, then you really need to have a conversation about how to safely treat her. At a minimum, I would treat the high axilla and the supraclavicular nodes because she had a pretty extensive lymph node dissection with more than 20 nodes, and then with her getting systemic therapy, that should be more than adequate.
Dr. Aggarwal. Is there any cutoff for age or size of the tumor where you would not do any radiation to the breast?
Dr. Manning. In this particular patient absolutely not because of the lymph node. She had breast-conserving therapy, and she’s only 32-years-old. The PRIME 2 study offered lumpectomy alone vs lumpectomy and radiation for women aged ≥ 65 years with tumors ≤ 3 cm, low grade.6 The study participants had to have negative lymph nodes, be ER+, and low grade. It was a very select group. The lumpectomy patients had a recurrence rate around 4%, and the other was closer to 1.3%.
You have to look at the whole picture. Is this a healthy 70-year-old woman? Is it an inconvenience for her to get treatment? Is she going to get hormone therapy and will she be adherent? There’s a very small group of women who underwent breast-conserving surgery that I would feel safe about not offering radiation.