Dr. Aggarwal. How common is a BRCA1 or BRCA2 mutation in African American females?
Ms. Venne. I have not paid attention to the prevalence of mutations based on ethnicity, so I don’t know. While many of the initial mutations were discovered in women of European ancestry, there are large cohorts of women with African ancestry whose specimens are now available for identifying genetic markers that will improve breast cancer risk assessment in them.1 However, because those mutations are still being characterized, it is more common to find a variant of uncertain significance (VUS) in African American women. A VUS is an alteration—a change in the gene—that we simply don’t know what it means yet. Clinicians don’t have enough information to know if that alteration is pathogenic or benign. The problem is that people try to make sense out of everything in their lives, so they also will try to make a VUS mean something. We try hard to help people understand that a VUS is really no more significant than if we had not tested in the first place, and they should not act on that information. They should use their family history, their age, their other psychosocial concerns about their experiences with cancer as they make their treatment decisions. But they also should check back periodically with their genetic counselor because VUSs can be reclassified. And if that happens, the information might be more useful for not only them, but their family members.
Dr. Manning. Would you consider this patient for any neoadjuvant chemotherapy?
Dr. Aggarwal. The patient is a young female with a small tumor that is HER2+. The indication for neoadjuvant chemotherapy is typically a big tumor or inoperable disease. Neoadjuvant chemotherapy is considered the standard of care for patients with inflammatory breast cancer and may confer a survival benefit in these patients. Of all the breast cancer subtypes, triple negative and HER2+ are considered the most chemosensitive and may benefit from neoadjuvant therapy. This patient has a small tumor, and I don’t think she’s a candidate for neoadjuvant chemotherapy unless the patient wants to see if her tumor is chemosensitive or not.
Dr. Manning, What’s the role and benefit of lumpectomy vs mastectomy?
Dr. Manning. Historically, mastectomy would have been considered the standard of care, but luckily, in the 1970s and the 1980s, we had a significant number of randomized controlled trials that demonstrated that certain women with particular characteristics would get the same overall survival if they chose mastectomy vs lumpectomy, the removal of the tumor with negative margin and whole-breast radiation. The key thing to understand is that breast-conserving surgery is now very well established with more than 20 years of data to support it. And that breast irradiation after breast-conserving surgery is essential to maximizing the local control and the overall survival (OS).
There have been a lot of major studies, but the one with the greatest follow-up now is the National Surgical Adjuvant Breast and Bowel Project (NSABP) B06 protocol, which was the only trial to compare mastectomy to lumpectomy and radiation or lumpectomy alone. It required negative margins. With 20 years of follow-up, the data still support that mastectomy or lumpectomy with radiation offers equivalent OS and local control. It’s really about patient preference if they are candidates.
Who is a candidate? Clearly, there are contraindications. We tend to look primarily at the size of the tumor. However, removing an average-sized tumor (< 2 cm) with a margin may not have a good cosmetic result for a patient with very small breasts. That patient may opt to go forward with a mastectomy instead. Young patients who are candidates must have to have negative margins. If they have persistently positive resection margins after excision or reexcision, then they need to go forward with mastectomy.
A patient who has imaging evidence of multicentric disease with 2 or more primary tumors in separate quadrants would not be a candidate for breast-conserving therapy. Diffuse malignant-appearing microcalcifications on a mammogram also would suggest multicentric disease. And a patient with a prior history of radiation therapy to the breast or chest wall cannot go through breast-conserving therapy.
In the case we are discussing, we also should make sure this young lady is not pregnant. If the patient is adamant about breast-conserving surgery and pregnant, especially in the third trimester, radiation could be deferred until after delivery. Another relative contraindication is for patients who have connective tissue disorders. Sometimes if they are given whole-breast radiation, the cosmetic result is poor. So if you’re doing this procedure to save the breast, then having a good cosmetic result is an important consideration for many patients.
When you look at the size of the tumor for this patient, she seems to be a good candidate for breast-conserving surgery. I would recommend that she go forward with lumpectomy followed by whole-breast radiation.