BRCA-positive breast cancer is associated with survival rates similar to those for BRCA-negative cancer in young women after treatment, according to a large, ongoing, prospective study in the U.K.
BRCA carriers with triple-negative breast cancer, however, may have a survival advantage over those without the mutation in the first few years after diagnosis, reported Diana M. Eccles, MD, of the University of Southampton School of Medicine, and colleagues in The Lancet Oncology.
“Women diagnosed with early breast cancer who carry a BRCA mutation are often offered double mastectomies soon after their diagnosis or chemotherapy treatment; however, our findings suggest that this surgery does not have to be immediately undertaken along with the other treatment,” Eccles said in a statement.
“In the longer term, risk-reducing surgery should be discussed as an option for BRCA1 mutation carriers in particular, to minimize their future risk of developing a new breast or ovarian cancer,” she added. “Decisions about timing of additional surgery to reduce future cancer risks should take into account patient prognosis after their first cancer, and their personal preferences.”
While only 5% of breast cancers are diagnosed in women under age 40, a significant proportion of deaths from breast cancer occur in this age group, including a high number who carry a pathogenic BRCA1 or BRCA2 mutation. Second primary breast cancers also are more frequent in high-risk gene carriers.
For the study, called POSH (Prospective Outcomes in Sporadic versus Hereditary), the researchers recruited female patients from 127 hospitals in the U.K. who were ages 18 to 40 when first diagnosed with invasive breast cancer, excluding those with a previous invasive malignancy. Recruitment stopped in 2008, and long-term follow-up is continuing.
All patients received treatment according to local protocols. Nearly 90% underwent chemotherapy. Half had breast-conserving surgery, and half had a mastectomy. The most common chemotherapy regimen was anthracycline, with or without taxanes.
The researchers examined detailed clinical follow-up information, including date and site of disease recurrence, at 6 months and 12 months, and then annually.
The primary outcome was overall survival — defined as the time from first diagnosis to death from any cause — comparing all BRCA1 or BRCA2 mutation carriers (BRCA-positive) with non-carriers (BRCA-negative). The secondary outcome was distant disease-free survival, defined as time from initial diagnosis to first distant disease.
Of 2,733 patients in the POSH analysis, 338 (12%) carried either a BRCA1 or BRCA2 mutation. Of the total sample, 558 women (20%) had triple-negative breast cancer. BRCA mutations were identified in 136 (24%) of patients with triple-negative breast cancer, and 123 of these women (90%) had a BRCA1 mutation.
The median follow-up was 8.2 years. In that period, 678 women died — 651 due to breast cancer.
The survival rates for both BRCA carriers and non-carriers were similar: after 2 years, the survival rates were 97% for carriers and 96.6% for non-carriers. After 5 years, the rates were 83.8% and 85%, and after 10 years, 73.4% versus 70.1%. Distant disease-free survival rates also were similar in both groups.
These results did not vary between unadjusted or adjusted analyses, including adjustments for ethnicity and body mass index.
Immediate bilateral mastectomy also was not associated with improved survival.
A subgroup analysis of 558 women with triple-negative breast cancer suggested that BRCA carriers initially may have better overall survival than women not carrying the mutation — 95% versus 91% at 2 years — but survival was similar at 5 or 10 years, for unclear reasons. This early survival advantage also has been seen in ovarian cancer patients who have the BRCA mutation, the authors noted.
Asked for her perspective, Virginia Kaklamani, MD, DSc, of the University of Texas Health Science Center at San Antonio, who was not involved in the study, said: “This is the largest prospective study looking at outcomes in BRCA-related breast cancer. Prior studies have shown some conflicting results regarding the breast cancer-related prognosis, but most have pointed to the fact that breast cancer outcomes are similar between BRCA carriers and non-carriers. This study confirms these findings.”
In an editorial accompanying the study, Peter Fasching, MD, of the Friedrich Alexander University Erlangen-Nuremberg in Germany, observed that while 338 patients in the POSH cohort had a BRCA1 or BRCA2 mutation, only 54% of the mutation carriers — 182 women — had been identified through routine healthcare.
“In most national and international guidelines, testing criteria include patients with breast cancer ages less than 35 or 40,” he wrote. “The fact that in the POSH study there were 155 young women diagnosed with breast cancer who did not know their mutation status raises the question of whether and when testing criteria for certain groups of patients can be allowed for lower mutation probabilities.”
Limitations of the study, the authors noted, included the fact that since it was restricted to women 40 or younger, the observations in young patients might not translate to women who were older when diagnosed. In addition, because triple-negative breast cancer was not well understood when the study was designed, it was therefore not powered for this as a primary outcome. Furthermore, breast cancer treatment recommendations in the U.K. also changed over the course of recruitment, which may have affected the survival rates.
The study was funded by Cancer Research UK, the UK National Cancer Research Network, the Wessex Cancer Trust, Breast Cancer Now, and the PPP Healthcare Medical Trust Grant.
The authors reported financial relationships with Roche, GSK, Pfizer, AstraZeneca, and Pierre Fabre.
F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner