Are symptomatic guidelines for chemotherapy appropriate to ER-positive screen-detected breast cancer (SDBC)?

Oncologists recommend chemotherapy to postmenopausal women with adverse prognostic factors, but predictors of the benefit of chemotherapy are mainly based on mortality from symptomatic cancer trials. From 1990 to 1998, 1475 breast cancers (875 screen detected cancers [SDBCs]: 600 symptomatic) were treated in women aged 50-65 years and prognostic factors compared with cancer mortality. Median follow-up was 110 months. The Nottingham Prognostic Index (NPI) was calculated for 6737 breast cancers which were part of the Association of Breast Surgery (ABS) 2001/2002 Audit of SDBCs to validate survival figures. Ten year survival was 92.1% for SDBC and 77.6% for symptomatic cancers. Adjusting for baseline factors, SDBCs had a reduced mortality (RR = 0.42 (0.31-0.57), independent of grade, node status and tumour size. Oestrogen receptor (ER) positive SDBC had a lower annual mortality rate (0.6%) compared with symptomatic (4.3%: P < 0.001) or ER negative SDBC (1.8%). Epithelial proliferation was lower in SDBC in all NPI groups compared with symptomatic cancers (P ≤ 0.001). Grade, node status, ER status, size and mode of detection predicted survival. Survival for each NPI group was better for SDBC. For ER positive SDBC in the Moderate Prognostic Group 1 (MPG1), 10 year mortality was 6.4% compared with 17.6% in symptomatic (P = 0.001). NPI on 6,737 operable SDBC confirmed similar mortality in all groups (4% mortality in MPG1 group). SDBC have lower mortality than symptomatic due to a lower proliferative index. The use of adjuvant chemotherapy is over-treatment for ER positive SDBCs with Good Prognostic Group (GPG) and MPG1 NPI scores.

Short-term biologic response to withdrawal of hormone replacement therapy in patients with invasive breast carcinoma.

BACKGROUND: The biologic effect of continuing hormone replacement therapy (HRT) after a diagnosis of breast carcinoma is unclear. The goal of rhe current study was to determine the short-term effect of HRT withdrawal on invasive breast carcinoma using biologic surrogate markers of tumor response. METHODS: The study was performed between 1996 and 2000 and comprised 140 women who had been using HRT at the time of breast carcinoma diagnosis by core needle biopsy. The breast tumors were removed a median of 17 days later (range, 2-31 days). Of these women, 125 women stopped HRT at the time of core needle biopsy and 15 continued to receive HRT until surgery. In addition, 55 women with breast carcinoma from the same time period, who were not receiving HRT at diagnosis, were studied. Changes in expression of Ki-67 (a measure of epithelial cell proliferation), progesterone receptor (PR), p27KIP-1 (a cyclin-dependent kinase inhibitor), and cyclin D1 (a cell cycle-related protein) were determined by immunohistochemistry on paired sections of the core needle biopsy and surgical specimens from each patient. RESULTS: In women who stopped HRT, a significant decrease in Ki-67 expression was observed between core needle biopsy and surgery in estrogen receptor (ER)-positive (n = 106; P < 0.001), but not in ER-negative tumors (n = 19; P = 0.58), with an associated reduction in PR (P < 0.001) and cyclin D1 expression (P < 0.001) and an increase in p27KIP-1 (P = 0.03). These changes in Ki-67 and PR expression occurred irrespective of c-erb-B2 status. No change was observed in any parameter in the other groups of patients. CONCLUSIONS: ER-positive invasive breast carcinomas demonstrated a favorable biologic response to withdrawal of HRT. Therefore, HRT should be stopped at the time of diagnosis and was subsequently contraindicated.