Initiation and tolerance of chemoprevention among women with high-risk breast lesions: the potential of low-dose tamoxifen

Bychkovsky, Brittany; Laws, Alison; Katlin, Fisher; Hans, Marybeth; Graichen, Mary; Pace, Lydia E.; Scheib, Rochelle; Garber, Judy E.; King, Tari A.

doi:10.1007/s10549-022-06577-5

Cited by 12 publications

(8 citation statements)

References 27 publications

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“…Second, the prevention in women with high-risk lesions, including ADH, atypical lobular hyperplasia, and LCIS, corroborates the recent chemopreventive strategies adopted by several centers that started offering low-dose tamoxifen. 5,6 Finally, the 64% significant reduction of the onset of contralateral breast cancer observed in our trial suggests a strong primary preventive potential in healthy women at high risk. Recent results from other groups are in line with this concept.…”

Section: Discussionsupporting

confidence: 53%

“…4 Recent data from US centers show that low-dose tamoxifen is the most popular choice of preventive therapy in women with high-risk lesions, with low discontinuation rates at 1 year compared with the standard dose and other preventive drugs. 5,6 To confirm the durability of the effect and assess long-term safety associated with 3 years of low-dose tamoxifen, here, we report the 10-year analyses of the TAM-01 trial .…”

Section: Introductionmentioning

confidence: 99%

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Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study

Lazzeroni

Puntoni

Guerrieri-Gonzaga

et al. 2023

JCO

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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results. METHODS We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS. RESULTS The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen v 19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank P = .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92; P = .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period. CONCLUSION Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study

Lazzeroni

Puntoni

Guerrieri-Gonzaga

et al. 2023

JCO

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“…This has been investigated in prevention studies with tamoxifen in women at high risk of developing breast cancer. Patients preferred low-dose tamoxifen over standard-dose tamoxifen in the preventive setting [ 89 , 90 ]. Furthermore, adherence rates were numerically higher for low-dose tamoxifen (93.3% vs. 85%), although this did not meet statistical significance [ 89 ].…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen Dose De-Escalation: An Effective Strategy for Reducing Adverse Effects?

Buijs,

Koolen,

Mathijssen

et al. 2024

Drugs

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Tamoxifen, a cornerstone in the adjuvant treatment of estrogen receptor-positive breast cancer, significantly reduces breast cancer recurrence and breast cancer mortality; however, its standard adjuvant dose of 20 mg daily presents challenges due to a broad spectrum of adverse effects, contributing to high discontinuation rates. Dose reductions of tamoxifen might be an option to reduce treatment-related toxicity, but large randomized controlled trials investigating the tolerability and, more importantly, efficacy of low-dose tamoxifen in the adjuvant setting are lacking. We conducted an extensive literature search to explore evidence on the tolerability and clinical efficacy of reduced doses of tamoxifen. In this review, we discuss two important topics regarding low-dose tamoxifen: (1) the incidence of adverse effects and quality of life among women using low-dose tamoxifen; and (2) the clinical efficacy of low-dose tamoxifen examined in the preventive setting and evaluated through the measurement of several efficacy derivatives. Moreover, practical tools for tamoxifen dose reductions in the adjuvant setting are provided and further research to establish optimal dosing strategies for individual patients are discussed.

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“…One-year discontinuation rates were nonsignificantly lower for those on tamoxifen 5 mg once daily compared with all other regimens (7% v 15%-20%). 11 Ongoing follow-up and other real-world data are needed in this area.…”

Section: Case 1: Clinical Challenges In Evaluation and Treatmentmentioning

confidence: 99%

Endocrine Therapy for Primary and Secondary Prevention After Diagnosis of High-Risk Breast Lesions or Preinvasive Breast Cancer

Laws

Punglia

2023

JCO

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The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. Patients with high-risk breast lesions (HRLs) or preinvasive breast cancers face an elevated risk of future breast cancer diagnoses. Endocrine therapy in this setting reduces the risk of a future diagnosis but does not confer improved survival, thus the side effects of primary/secondary prevention must be considered relative to the benefits. Here, we discuss the available chemoprevention regimens for patients with HRLs and considerations for selecting a regimen, as well as the decision making surrounding use of adjuvant endocrine therapy for patients with ductal carcinoma in situ (DCIS). For patients with HRLs, available chemoprevention regimens differ by menopausal status, including tamoxifen 20 mg once daily for 5 years and more recently tamoxifen 5 mg once daily for 3 years in both premenopausal and postmenopausal women as well as raloxifene or aromatase inhibitors for postmenopausal women. We recommend a shared decision-making approach with attention to patient preferences related to risk tolerance and side-effect profiles. Low-dose tamoxifen appears to be a particularly favorable choice that is well tolerated, without risk of serious adverse events and offers comparable risk reduction to other regimens. For DCIS, the benefit of endocrine therapy in addition to radiation is small, and appears to be driven mainly by a reduction in contralateral breast diagnoses or new breast cancers. A strategy that reduces the side-effect profile of chemoprevention such as low-dose tamoxifen may be especially appealing in the setting of secondary prevention.

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Initiation and tolerance of chemoprevention among women with high-risk breast lesions: the potential of low-dose tamoxifen

Cited by 12 publications

References 27 publications

Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study

Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study

Tamoxifen Dose De-Escalation: An Effective Strategy for Reducing Adverse Effects?

Endocrine Therapy for Primary and Secondary Prevention After Diagnosis of High-Risk Breast Lesions or Preinvasive Breast Cancer

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