Mammographic Density Reduction Is a Prognostic Marker of Response to Adjuvant Tamoxifen Therapy in Postmenopausal Patients With Breast Cancer

Purpose Tamoxifen treatment is associated with a reduction in mammographic density and an improved survival. However, the extent to which change in mammographic density during adjuvant tamoxifen therapy can be used to measure response to treatment is unknown. Patients and Methods Overall, 974 postmenopausal patients with breast cancer who had both a baseline and a follow-up mammogram were eligible for analysis. On the basis of treatment information abstracted from medical records, 474 patients received tamoxifen treatment and 500 did not. Mammographic density was measured by using an automated thresholding method and expressed as absolute dense area. Change in mammographic density was calculated as percentage change from baseline. Survival analysis was performed by using delayed-entry Cox proportional hazards regression models, with death as a result of breast cancer as the end point. Analyses were adjusted for a range of patient and tumor characteristics. Results During a 15-year follow-up, 121 patients (12.4%) died from breast cancer. Women treated with tamoxifen who experienced a relative density reduction of more than 20% between baseline and first follow-up mammogram had a reduced risk of death as a result of breast cancer of 50% (hazard ratio, 0.50; 95% CI, 0.27 to 0.93) compared with women with stable mammographic density. In the no-tamoxifen group, there was no statistically significant association between mammographic density change and survival. The survival advantage was not observed when absolute dense areas at baseline or follow-up were evaluated separately. Conclusion A decrease in mammographic density after breast cancer diagnosis appears to serve as a prognostic marker for improved long-term survival in patients receiving adjuvant tamoxifen, and these data should be externally validated.

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Adverse effects of adjuvant tamoxifen treatment on bone mineral density in premenopausal breast cancer patients: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12500 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12500-e12500

Author(s):

Chihwan Cha ◽

Soo Jin Lee ◽

Hanpyo Hong ◽

Yun Young Choi ◽

Min Sung Chung

Keyword(s):

Breast Cancer ◽

Lumbar Spine ◽

Bone Loss ◽

Meta Analysis ◽

Premenopausal Women ◽

Tamoxifen Therapy ◽

Tamoxifen Treatment ◽

Adjuvant Tamoxifen ◽

Mineral Density ◽

Adjuvant Tamoxifen Therapy

e12500 Background: It is well known that adjuvant tamoxifen treatment for breast cancer in postmenopausal women decreases bone loss. However, the adverse effect of adjuvant tamoxifen therapy for bone mineral density (BMD) in premenopausal breast cancer patients remains uncertain. This meta-analysis aimed to assess the effects of adjuvant tamoxifen therapy on BMD changes in premenopausal women with primary breast cancer. Methods: Through April 2020, studies reporting BMD changes of lumbar spine or hip in premenopausal women with primary breast cancer treated with adjuvant tamoxifen were collected from EMBASE and PubMed. The pooled analysis was performed using random effects model of the standardized mean difference (SMD) of BMD in patients. Results: A total of 1,432 premenopausal patients from eight studies were included in the pooled analysis. After 3 years of median follow up, adjuvant tamoxifen therapy decreased BMD by as much as SMD of -0.79 [95% confidence interval (CI); -1.25 to -0.33, P < 0.01] at lumbar spines and -0.38 at hip (95%CI; -0.88 to 0.12, P > 0.05). Compared with patients received tamoxifen alone, patients who received combination therapy with chemotherapy or ovarian function suppression (OFS) showed decreased bone loss at lumbar spine (SMD -1.17 with 95%CI -1.59 to -0.75, -0.43 with 95%CI -2.26 to 1.40, and -0.75 with 95%CI -1.38 to -0.13, respectively). Conclusions: Our meta-analysis revealed that premenopausal women who received adjuvant tamoxifen treatment showed significant bone loss over a period of time, especially at lumbar spine. However, tamoxifen attenuated bone loss in those who received tamoxifen after chemotherapy or along with OFS.[Table: see text]

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Prognostic impact of co-expression of LLCL2 and SLC7A5 in ERα-positive breast cancer patients

10.21203/rs.3.rs-728950/v1 ◽

2021 ◽

Author(s):

Tomoka Hisada ◽

Naoto Kondo ◽

Yumi Wanifuchi-Endo ◽

Satoshi Osaga ◽

Takashi Fujita ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Endocrine Therapy ◽

Tamoxifen Therapy ◽

Adjuvant Tamoxifen ◽

Positive Trend ◽

Breast Cancer Patients ◽

Adjuvant Tamoxifen Therapy ◽

Positive Breast Cancer

Abstract Background Lethal giant larvae homolog 2 (LLGL2) functions as a promoter of tumor growth and localizes at cell junctions and membranes with solute carrier family 7 member 5 (SLC7A5) in estrogen receptor α (ERα)-positive breast cancer. LLGL2 and SLC7A5 have been reported to be involved in resistance to endocrine therapy. This study aimed to assess the effects of LLGL2/SLC7A5 co-expression in predicting prognosis and response to endocrine therapy in ERα-positive breast cancer patients. Methods The associations of clinicopathological factors with LLGL2 and SLC7A5 expression or LLGL2/SLC7A5 co-expression at the mRNA and protein level were assessed in invasive breast cancer patients with long-term follow-up. The median follow-up period was approximately10 years. Survival curves were analyzed using the Kaplan–Meier method and verified by the log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values using stepwise linear regression. Results We identified a positive association between low mRNA expression of LLGL2 or SLC7A5 alone and longer disease-free survival (DFS) and overall survival (OS) in ERα-positive breast cancer patients, but not in ERα-negative patients. We also identified that low LLGL2/SLC7A5 mRNA co-expression (LLGL2low/SLC7A5low) was associated with longer survival compared with other combination groups in all breast cancer patients. In ERα-positive breast cancer patients, LLGL2low/SLC7A5low showed longer survival compared with LLGL2high/SLC7A5high and a positive trend of longer survival compared with other combination groups. We also observed that LLGL2low/SLC7A5low showed longer survival compared with LLGL2high/SLC7A5high in ERα-positive breast cancer patients receiving adjuvant tamoxifen therapy. Multivariate analysis demonstrated that LLGL2low/SLC7A5low was an independent favorable prognostic factor of both DFS and OS in ERα-positive breast cancer patients. High co-expression of LLGL2 and SLC7A5 protein showed a positive trend of shorter survival. Conclusions Our study showed that co-expression of LLGL2 and SLC7A5 mRNA is a promising candidate biomarker and suggested that the LLGL2–SLC7A5 axis may be a therapeutic target in early breast cancer patients, especially in those receiving adjuvant tamoxifen therapy.

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