SABCS 2019: hormone-receptor-positive breast cancer, adjuvant chemotherapy, and prevention
Preventing breast cancer (BC) is still one of the most important goals for those physicians working with women who are at higher risk to suffer from BC. Trials such as the IBIS‑I [
1], the STAR Trial [
2], the Royal Marsden Prevention Trial [
3] and the NSABP-P1 [
4] showed that women treated with SERMs (Selective Estrogen Receptor Modulator) like tamoxifen (TAM) and raloxifen do not to develop invasive BC. Two presentations at the SABCS 2019 dealt with this topic.
Randomized trial of low-dose tamoxifen to prevent recurrence of breast intraepithelial neoplasia. Study TAM01 [5]
Women with premalignant diseases (ADH, LCIS, DCIS), increased risk (Gail, BCSC), gene mutation carriers, prior radiation and hormone replacement therapy (HRT) users or obese women should be treated in order to prevent BC. TAM lowers overdiagnosis by 30% in high-risk women undergoing screening mammography [
6]. Reduction in breast density during intake of TAM could present one potential predictive marker for prevention [
7]. If women show more than 10% of reduction in mammographic density after 1 year they should continue with therapy.
As we already saw in the past, there was no disadvantage of using low-dose TAM in presurgical trials in order to reduce Ki-67. The presented trial randomized women aged less than 75 years and at higher risk for breast cancer into two arms comparing TAM 5 mg/day (babytam) vs. placebo. The primary endpoint was the incidence of invasive BC or DCIS.
All breast events decreased by 50% (28 vs. 14) in the babytam group and contralateral breast cancer decreased by 75% (12 vs. 3) with almost identical treatment adherence in both arms (TAM 64.8% vs. placebo 60.7%).
Long-term results of the International Breast Cancer Intervention Study II (IBIS-II) using anastrozole [8]
As the IBIS-II and MAP.3 trials have already shown an impact of aromatase inhibitors (AI) on breast cancer incidence in high-risk postmenopausal women, Cuzick et al. gave a 60 month update with a special focus on the posttreatment period.
Postmenopausal women aged 40–70 years at increased risk for BC received either anastrozole (ANA) or placebo for 5 years and had a median follow-up of almost 11 years.
The BC incidence after 5 years was 4.6% for placebo vs 1.8% for ANA (HR 0.39) and 8.8% for placebo vs. 5.3% for ANA after 12 years (HR 0.51). These results where even more impressive than in the IBIS‑I trial (TAM vs placebo HR 0.72). Adherence to treatment was similar (77.0% placebo vs. 74.6% ANA; HR 0.89).
NSABP B-42: extended adjuvant endocrine treatment with letrozole [9]
The 10-year results demonstrate a statistically significant improvement in DFS with extended letrozole (LET): 16% reduction in DFS events and 4% absolute improvement. There was no significant difference in OS with LET vs. placebo. Extended LET provided statistically significant improvement in BCFI. LET did not significantly increase the risk of osteoporotic fractures or thrombotic events.
Validation of the clinical treatment score post 5 years (CTS5) in women with HR positive, HER2 negative, node negative disease from the TAILORx study [10]
As there is a known continued risk of late recurrence in HR positive disease, the CTS5 score was developed to predict late distant recurrence by involving nodal status, tumor size, tumor grade, and age. Women aged 18–75 years with luminal A breast cancer who were distant recurrence free after 5 years were investigated.
Menopausal hormone therapy and breast cancer: long-term findings from the Women’s Health Initiative randomized clinical trials [11]
After more than 50 years, the influence of hormone therapy on breast cancer remains controversial with discordant findings from observational studies to randomized clinical trials. Patients with or without hysterectomy were randomized either to receive CEE (conjugated equine estrogen) with or without progestrone (MPA) vs. placebo.
Adjuvant endocrine therapy in 2020: it’s complicated [12]
This presentation summarized all essential topics concerning treatment of hormone receptor positive BC.
Addition of S‑1 to endocrine adjuvant treatment—Potent trial [13]
S‑1 is a combination drug based on biochemical modification of fluorouracil, containing tegafur, gimneracil, and oteracil. S‑1 is administered twice a day for 14 days and 7 days off for 1 year. Patients at intermediate or higher risk of recurrence who would be candidates for additional adjuvant chemotherapy or who already had neoadjuvant treatment were randomized after surgery either to receive S‑1 + endocrine therapy vs. endocrine therapy alone.
Primary endpoint was iDFS. Secondary endpoints were OS, DFS, and safety.
Effects of capecitabine as part of neo/adjuvant chemotherapy
The primary objective of this analysis was to examine the effect of capecitabine (CAP) on DFS. Secondary objectives were the effect on OS and to test if there is an interaction of occurrence of capecitabine-specific toxicity and treatment effects. Median follow-up of this examination was 79 months.
Overall CAP did not alter DFS in this meta-analysis, but when it was administered in addition to other systemic treatment an improvement in DFS was observed. OS was improved by CAP treatment in the overall cohort and when given in addition. Only patients with triple negative breast cancer (TNBC) benefited from treatment with CAP overall and in addition to other systemic therapy in terms of DFS and OS. All effects were small; the largest was observed for OS in patients with TNBC who received capecitabine in addition (HR 0.78). There was no evidence supporting a predictive value of capecitabine-specific adverse events on patient outcome.
CBCSG-10
Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for TNBC [17]
Patients with TNBC received three cycles of docetaxel with or without CAP and were then switched to either receive FEC or EC in combination with CAP (1000 mg/m2 bid).
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