Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial

Mustacchi, Giorgio; Ceccherini, Rita; Milani, Stefano; Pluchinotta, Alfonso M.; Matteis, A. De; Maiorino, Luigi; Farris, A.; Scanni, A.; Sasso, Franco

doi:10.1093/annonc/mdg117

Cited by 197 publications

(106 citation statements)

References 21 publications

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“…None of the studies evaluated the oestrogen receptor status of the women they recruited. Four eligible trials addressing surgery plus endocrine therapy vs primary endocrine therapy were identified, of which three have reported outcome data (Willsher et al, 1997;Capasso et al, 2000;Mustacchi et al, 2003;Fennessey et al, 2004), although there is currently no data from one in a form that can be meta-analysed (Capasso et al, 2000). Not all trials identified provided adequate information on all outcomes.…”

Section: Resultsmentioning

confidence: 99%

“…The quality of three trials was graded as A (Fentiman et al, 2003;Mustacchi et al, 2003;Fennessey et al, 2004) with the rest being graded as B (Gazet et al, 1994;Willsher et al, 1997;Kenny et al, 1998;Capasso et al, 2000). No potentially eligible study was excluded from the review.…”

Section: Resultsmentioning

confidence: 99%

“…Three trials (1076 women: Willsher et al, 1997; Mustacchi et al, 2003;Fennessey et al, 2004) reported data on OS which could be meta-analysed. There was a nonsignificant trend in favour of surgery plus endocrine therapy (HR 0.86, 95% CI 0.73 -1.00, P ¼ 0.06).…”

Section: Resultsmentioning

confidence: 99%

“…There was a nonsignificant trend in favour of surgery plus endocrine therapy (HR 0.86, 95% CI 0.73 -1.00, P ¼ 0.06). Only one trial (474 women: Mustacchi et al, 2003) reported adequate data on PFS to calculate a significant difference favouring surgery plus endocrine therapy (HR 0.65, 95% CI 0.53 -0.81, P ¼ 0.0001). In the surgery arm, 59% of women died or progressed compared to 80% in the tamoxifen There was significant heterogeneity between the two studies (w 2 2.90, Po0.09, I 2 65.6%), which is discussed below, although each individually showed a statistically significant difference in treatment effect favouring the surgery arm.…”

Section: Resultsmentioning

confidence: 99%

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Surgery, with or without tamoxifen, vs tamoxifen alone for older women with operable breast cancer: Cochrane review

2007

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The published literature comparing surgery, with or without adjuvant endocrine therapy, with endocrine therapy alone in older women with operable breast cancer was systematically reviewed.The design used is Cochrane review. Randomised controlled trials retrieved from the Cochrane Breast Cancer Group Specialised Register on 29 June 2005. Eligible studies recruited women aged 70 years or over with operable breast cancer, fit for surgery under general anaesthia. The studies compared surgery (either mastectomy or wide local excision, with or without endocrine therapy) to endocrine therapy alone. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Double data extraction and quality assessment were undertaken. Seven eligible trials were identified of which six had published time-to-event data. The quality of the allocation concealment was adequate in three studies and unclear in the remainder. In each case the endocrine therapy used was tamoxifen. When surgery alone was compared to endocrine therapy alone, there was no significant difference in OS (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.74 -1.30, P ¼ 0.9), but a significant difference in PFS (HR 0.55, 95% CI 0.39 -0.77, P ¼ 0.0006). When surgery with adjuvant endocrine therapy was compared to endocrine therapy alone, there was no significant difference in OS (HR 0.86, 95% CI 0.73 -1.00, P ¼ 0.06), but a significant difference in PFS (HR 0.65 (95% CI 0.53 -0.81, P ¼ 0.0001) for surgery plus endocrine therapy vs primary endocrine. The regimens have different side effect profiles with one study suggesting increased psychosocial morbidity at 3 months in the surgical arm, which resolves by 2 years. Primary endocrine therapy with tamoxifen is associated with inferior local disease control but noninferior survival to surgery for breast cancer in older women. Trials are needed to evaluate appropriate selection criteria for its use in terms of patient co-morbidity and quality of life. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for this population.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Surgery, with or without tamoxifen, vs tamoxifen alone for older women with operable breast cancer: Cochrane review

2007

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“…tamoxifen as sole treatment) in older women. However, the five randomised controlled trials which have compared tamoxifen vs surgery have demonstrated better local control with surgery than with tamoxifen (Robertson et al, 1992;Gazet et al, 1994;Bates et al, 2001;Fentiman et al, 2003;Mustacchi et al, 2003). However, only one of these studies showed a reduction in survival with tamoxifen after 12 years of follow-up (Bates et al, 2001).…”

Section: Primary Endocrine Therapymentioning

confidence: 99%

Stage and treatment variation with age in postmenopausal women with breast cancer: compliance with guidelines

et al. 2004

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Breast cancer-specific mortality is static in older women despite having fallen in younger age groups, possibly due to lack of screening and differences in treatment. This study compared stage and treatment between two cohorts of postmenopausal women (55 -69 vs 470 years) in a single cancer network over 6 months. A total of 378 patients were studied (470: N ¼ 167, 55 -69 years: N ¼ 210). Older women presented with more advanced disease (470: metastatic/locally advanced 12%, 55 -69 years: 3%, Po0.01). Those with operable cancer had a worse prognosis (Nottingham Prognostic Index (NPI) 470: median NPI 4.4, 55 -69 years: 4.25, Po0.03). These stage differences were partially explained by higher screening rates in the younger cohort. Primary endocrine therapy was used in 42% of older patients compared with 3% in the younger group (Po0.001). Older women with cancers suitable for breast conservation were more likely to choose mastectomy (470: 57.5% mastectomy rate vs 55 -69 years: 20.6%, Po0.01). Nodal surgery was less frequent in older patients (470: 6.7% no nodal surgery, 55 -69 years: 0.5%, Po0.01) and was more likely to be inadequate (470: 10.7% o4 nodes excised, 55 -69 years: 3.4%, Po0.02). In summary, older women presented with more advanced breast cancer, than younger postmenopausal women and were treated less comprehensively.

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Neoadjuvant Endocrine Therapy for Estrogen Receptor–Positive Breast Cancer

et al. 2016

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IMPORTANCE Estrogen receptor-positive (ER+) tumors of the breast are generally highly responsive to endocrine treatment. Although endocrine therapy is the mainstay of adjuvant treatment for ER+ breast cancer, the role of endocrine therapy in the neoadjuvant setting is unclear. OBJECTIVE To evaluate the effect of neoadjuvant endocrine therapy (NET) on the response rate and the rate of breast conservation surgery (BCS) for ER+ breast cancer. DATA SOURCES Based on PRISMA guidelines, a librarian-led search of PubMed and Ovid MEDLINE was performed to identify eligible trials published from inception to May 15, 2015. The search was performed in May 2015. STUDY SELECTION Inclusion criteria were prospective, randomized, neoadjuvant clinical trials that reported response rates with at least 1 arm incorporating NET (n = 20). Two authors independently analyzed the studies for inclusion. DATA EXTRACTION AND SYNTHESIS Pooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model. RESULTS The analysis included 20 studies with 3490 unique patients. Compared with combination chemotherapy, NET as monotherapy with aromatase inhibitors had a similar clinical response rate (OR, 1.08; 95% CI, 0.50–2.35; P = .85; n = 378), radiological response rate (OR, 1.38; 95% CI, 0.92–2.07; P = .12; n = 378), and BCS rate (OR, 0.65; 95% CI, 0.41–1.03; P = .07; n = 334) but with lower toxicity. Aromatase inhibitors were associated with a significantly higher clinical response rate (OR, 1.69; 95% CI, 1.36–2.10; P < .001; n = 1352), radiological response rate (OR, 1.49; 95% CI, 1.18–1.89; P < .001; n = 1418), and BCS rate (OR, 1.62; 95% CI, 1.24–2.12; P < .001; n = 918) compared with tamoxifen. Dual combination therapy with growth factor pathway inhibitors was associated with a higher radiological response rate (OR, 1.59; 95% CI, 1.04–2.43; P = .03; n = 355), but not clinical response rate (OR, 0.76; 95% CI, 0.54–1.07; P = .11; n = 537), compared with endocrine monotherapy. The incidence of pathologic complete response was low (<10%). CONCLUSIONS AND RELEVANCE Neoadjuvant endocrine therapy, even as monotherapy, is associated with similar response rates as neoadjuvant combination chemotherapy but with significantly lower toxicity, suggesting that NET needs to be reconsidered as a potential option in the appropriate setting. Additional research is needed to develop rational NET combinations and predictive biomarkers to personalize the optimal neoadjuvant strategy for ER+ breast cancer.

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Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial

Cited by 197 publications

References 21 publications

Surgery, with or without tamoxifen, vs tamoxifen alone for older women with operable breast cancer: Cochrane review

Surgery, with or without tamoxifen, vs tamoxifen alone for older women with operable breast cancer: Cochrane review

Stage and treatment variation with age in postmenopausal women with breast cancer: compliance with guidelines

Neoadjuvant Endocrine Therapy for Estrogen Receptor–Positive Breast Cancer

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