SAN ANTONIO – In a global study involving more than 5,000 women, risk-reducing surgeries significantly improved survival and lowered the risk of cancer recurrence in women who harbor BRCA1/2 mutations and developed cancer at a young age.
The study, presented at the San Antonio Breast Cancer Symposium on Wednesday, explored the potential benefit of risk-reducing mastectomy or oophorectomy in BRCA1/2-mutant patients who were diagnosed with breast cancer before or at age 40.
Matteo Lambertini, associate professor and consultant in medical oncology at the University of Genova-IRCCS Policlinico San Martino Hospital in Genova, Italy, presented the results at the meeting and said this is the first study to explore the effect of risk-reducing surgeries in young breast cancer patients.
"In BRCA carriers with prior diagnosis of breast cancer, additional challenges should be considered [before recommending a risk-reducing surgery], particularly for young patients," Lambertini said. "When we counsel specifically young patients, we should keep in mind that these surgical interventions may have an important impact on [their] reproductive plans and quality of life."
Researchers evaluated overall survival, disease-free survival, and breast cancer-free interval in patients who did and did not undergo mastectomy or oophorectomy. A total of 2,910 patients, or 55 percent, underwent mastectomies and 2,782 patients, 52.6 percent, in the study underwent oophorectomies. Also, 1,804 patients, or 34.1 percent, underwent both procedures.
The median time from breast cancer diagnosis to surgery was 0.8 years for risk-reducing mastectomies and three years for risk-reducing oophorectomies.
Among patients who underwent a mastectomy, there was a 35 percent reduction in the risk of death compared to those who did not undergo the surgery. Researchers followed patients for a median 5.1 years to determine survival and recurrence outcomes after surgery. Those who had a mastectomy had more than a 40 percent lower risk of developing any cancer, including a breast cancer recurrence, compared to those who didn't have this surgery, Lambertini said.
The benefit was similar across all subgroups analyzed, he noted. Patients were evaluated based on whether they had BRCA1 or BRCA2 mutations, as well as their age at diagnosis, tumor subtype, tumor size, nodal status, prior chemotherapy, timing of BRCA testing, and residence in a high- or low-income country.
Among patients who underwent an oophorectomy, there was a significant improvement in overall survival, according to Lambertini, with a 42 percent reduction in the risk of death compared to those who didn't have an oophorectomy. Similarly, these patients also had a 30 percent lower risk of developing another cancer or experiencing breast cancer recurrence. Researchers followed patients in this group for a median 4.9 years to track survival and recurrence outcomes.
The researchers reported a greater benefit with oophorectomy among patients with BRCA1 mutations and triple-negative breast cancer. In the TNBC group, the reduction in the risk of death was more than 80 percent.
"The explanation is probably related to the specific [risks associated with the] BRCA1 gene," Lambertini said, pointing out that BRCA1 mutation carriers mostly develop triple-negative breast cancer while BRCA2 mutation carriers have different risks. "The risk of ovarian cancer is lower in BRCA2 carriers compared to BRCA1, and the patient population in our study is very young, and the risk of ovarian cancer in BRCA2 carriers is higher with age."
The researchers also found that the benefit of oophorectomy on disease-free survival and breast cancer recurrence was more pronounced among patients who also underwent mastectomy.
However, when the researchers compared survival outcomes for those who received one surgery but not the other, they found there wasn't a statistically significant difference, suggesting oophorectomy and mastectomy had an independent effect on a patient's survival.
Lambertini emphasized that the findings from this study are only informative for guiding treatment for this specific patient population: BRCA1/2 mutation carriers with young-onset breast cancer. Physicians should not use these data to inform preventive care for BRCA1/2 mutation carriers who've never had breast cancer or who are diagnosed with breast cancer at an older age, he said.
Kate Lathrop, director of the medical oncology and hematology fellowship program at the University of Texas Health Science Center at San Antonio, said at a press conference at SABCS that these data will help doctors discuss with young breast cancer patients, especially those who are concerned about removing their ovaries, the cancer risk reduction they can expect with these surgeries. "These are women who are still potentially in a reproductive stage of life, [and they] have to balance" their needs and reduce their cancer risk, she said.