Long-term outcome of invasive breast cancer.

Sir—László Tabár and colleagues (Feb 5, p 429) report striking results about a novel prognostic factor in breast cancers of small size. Currently, the proportion of small breast cancers diagnosed is increasing as a result of large-scale mammographic screening. However, the selection of women who will benefit from adjuvant treatment remains a challenge. Also, prognostic factors for breast-cancer outcome, such as involvement of axillary lymph nodes or high-grade tumours, have not been consistently reported as useful for small tumours. In their prospective study of invasive breast cancers of less than 15 mm diameter, Tabár and colleagues showed that casting-type calcification, when present on a diagnostic mammogram, was associated with a significantly worse survival. Comedocarcinoma results in casting-type mammographic calcifications and is associated with residual microscopic disease, local recurrence, and high-grade invasive cancer. All these features could negatively influence outcome. By contrast, little is known about the influence of host factors on outcome. To address this question, we did an ethnically restricted retrospective study. We studied 85 consecutive pathology blocks from Ashkenazi Jewish women under the age of 65 years, who had been diagnosed between 1986 and 1995 with breast cancers of less than 15 mm diameter. All except one (99%) patient were treated by breast conservative surgery and 29 (34%) patients received adjuvant chemotherapy. After recording histopathological variables, DNA was extracted from tumours and tested for the presence of the three common founder mutations present in Ashkenazi Jewish women in the breast-cancer predisposing genes BRCA1 and BRCA2. Ten (11·8%) BRCA1 and two (2·4%) BRCA2 mutation carriers were identified. Breast-cancer-specific survival was assessed after a median follow-up of 88 months. Seven breast-cancer deaths were recorded. As reported by Tabár and colleagues, axillary lymph-node status was not identified as a prognostic factor (p=0·8) and nuclear grade was of borderline significance (p=0·08). The strongest outcome predictor was the BRCA1/2 mutation carrier status. At the median follow-up, breast-cancerspecific survival for BRCA1/2 mutation carriers was 60% versus 95% for women without BRCA1/2 mutations (p<0·0001). The numbers are small, but these findings suggest that BRCA1/2 mutation status, which is a risk for breast cancer that is present at birth, has a significant impact on outcome, even when tumours are very small. It is uncertain whether or not BRCA1/2associated breast cancer is associated with ductal carcinoma in situ (DCIS). In our series, none of the 12 BRCA1/2-associated breast cancers was associated with comedo-type or had an important component of DCIS, compared with 17 of 73 nonBRCA1/2 tumours. Our findings suggest that prevention will be particularly important for BRCA1/2 mutation carriers because mammography is unlikely to detect serious preinvasive disease and the outcome following small invasive breast cancers is surprisingly poor.