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

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

doi:10.1007/s10549-022-06577-5

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

Breast Cancer Res Treat. 2022 Jun;193(2):417-427. doi: 10.1007/s10549-022-06577-5. Epub 2022 Apr 4.

Authors

Brittany Bychkovsky^{1

2

3}, Alison Laws^{1

2

4}, Fisher Katlin⁴, Marybeth Hans⁴, Mary Knust Graichen⁴, Lydia E Pace^{1

5}, Rochelle Scheib^{1

2

3}, Judy E Garber^{1

2

3}, Tari A King^{6

7

8}

Affiliations

¹ Harvard Medical School, Boston, MA, USA.
² Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
³ Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, USA.
⁴ Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
⁵ Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁶ Harvard Medical School, Boston, MA, USA. Tking7@bwh.harvard.edu.
⁷ Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA. Tking7@bwh.harvard.edu.
⁸ Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA. Tking7@bwh.harvard.edu.

Abstract

Purpose: High-risk lesions (HRLs) of the breast are an indication for chemoprevention, yet uptake is low, largely due to concerns about side effects. In 2019, low-dose (5 mg) tamoxifen was demonstrated to reduce breast cancer risk with improved tolerance. We describe chemoprevention uptake in an academic clinic before and after the introduction of low-dose tamoxifen.

Methods: Females age ≥ 35 with HRLs who established care from April 2017 through January 2020 and eligible for chemoprevention were included. Rates of chemoprevention initiation before and after the introduction of low-dose tamoxifen (pre-2019 vs. post-2019) were compared with chi-squared tests. Logistic regression identified demographic and clinical factors associated with chemoprevention initiation. Kaplan-Meier methods determined the rates of discontinuation.

Results: Among 660 eligible females with HRLs, 22.7% initiated chemoprevention. Median time from first visit to chemoprevention initiation was 54 days (interquartile range (IQR): 0-209); 31.0% (46/150) started chemoprevention > 6 months after their initial visit. Chemoprevention uptake was not significantly different pre-2019 vs. post-2019 (21.2% vs. 26.3%, p = 0.16); however, post-2019, low-dose tamoxifen became the most popular option (41.5%, 34/82). On multivariable analyses, age and breast cancer family history were significantly associated with chemoprevention initiation. Discontinuation rates at 1 year were lowest for low-dose tamoxifen (6.7%) vs. tamoxifen 20 mg (15.0%), raloxifene (20.4%), or an aromatase inhibitor (20.0%).

Conclusion: In this modern cohort, 22.7% of females with HRLs initiated chemoprevention with 31.0% initiating chemoprevention > 6 months after their first visit. Low-dose tamoxifen is now the most popular choice for chemoprevention, with low discontinuation rates at 1 year.

Keywords: Atypical ductal hyperplasia (ADH); Atypical lobular hyperplasia (ALH); Chemoprevention; High-risk lesions; Lobular carcinoma in situ (LCIS); Low-dose tamoxifen.

MeSH terms

Aromatase Inhibitors / therapeutic use
Breast Neoplasms* / drug therapy
Breast Neoplasms* / epidemiology
Breast Neoplasms* / prevention & control
Chemoprevention / methods
Female
Humans
Male
Raloxifene Hydrochloride / adverse effects
Tamoxifen* / adverse effects

Substances

Aromatase Inhibitors
Tamoxifen
Raloxifene Hydrochloride