Underlying Breast Cancer Risk and Menopausal Hormone Therapy

2020 ◽  
Vol 105 (6) ◽  
pp. e2299-e2307 ◽  
Author(s):  
Richard J Santen ◽  
Daniel F Heitjan ◽  
Anne Gompel ◽  
Mary Ann Lumsden ◽  
JoAnn V Pinkerton ◽  
...  

Abstract The recent Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC) publication calculated the attributable risk of breast cancer from use of estrogen alone and estrogen plus a synthetic progestogen for less than 5 to 15 or more years of use. This CGHFB report calculated attributable risk based on their findings of relative risk from pooled data from 58 studies. Notably, neither the CGHFBC nor other previous studies have examined the effect of underlying risk of breast cancer on attributable risk. This omission prompted us to determine the magnitude of the effect of underlying risk on attributable risk in this perspective. Meaningful communication of the potential risk of menopausal hormonal therapy requires providing women with the estimated risk above their existing underlying risk (ie, attributable risk). Therefore, we have estimated attributable risks from the data published by the CGHFBC, taking into account varying degrees of underlying risk. Based on the Endocrine Society Guideline on Menopausal Hormone Therapy (MHT), we divided groups into 3 categories of risk: low (1.5%), intermediate (3.0%), and high (6.0%) underlying risk of breast cancer over 5 years. In women taking estrogen plus a synthetic progestogen for 5 to 9 years, the attributable risks of MHT increased from 12, to 42, to 85 additional women per 1000 in the low-, intermediate-, and high-risk groups, respectively. The attributable risks for estrogen alone were lower but also increased based on underlying risk. Notably, the attributable risks were amplified with duration of MHT use, which increased both relative risk and breast cancer incidence.

The Breast ◽  
2010 ◽  
Vol 19 (3) ◽  
pp. 198-201 ◽  
Author(s):  
Claudio Pelucchi ◽  
Fabio Levi ◽  
Carlo La Vecchia

Maturitas ◽  
2016 ◽  
Vol 84 ◽  
pp. 81-88 ◽  
Author(s):  
Caroline Antoine ◽  
Lieveke Ameye ◽  
Marianne Paesmans ◽  
Evandro de Azambuja ◽  
Serge Rozenberg

Endocrinology ◽  
2012 ◽  
Vol 154 (2) ◽  
pp. 656-665 ◽  
Author(s):  
Yan Song ◽  
Richard J. Santen ◽  
Ji-ping Wang ◽  
Wei Yue

Breast cancer incidence is increased in women receiving menopausal hormone therapy with estrogen plus progestin but not with estrogen alone. The use of a tissue-selective estrogen complex (TSEC) has been proposed as a novel menopausal hormone therapy strategy to eliminate the requirement for a progestogen. Combination of bazedoxifene (BZA) with conjugated estrogens (CEs), the first TSEC, has shown beneficial effects. Whether it would exert antiestrogenic effects on breast cancer is not clear. To address this issue, we compared estradiol (E2) and CE alone on proliferation and apoptosis in MCF-7 breast cancer cells. CE stimulated growth of MCF-7 cells at a peak concentration 10-fold higher than required for E2. Both CE and E2 alone increased DNA synthesis and reduced apoptosis with activation of MAPK, Akt, and p70S6K and up-regulation of antiapoptotic factors survivin, Bcl-2, and X-linked inhibitor of apoptosis protein, These effects could be completely blocked by BZA. Gene expression studies demonstrated that CE and E2 were equally potent on expression of cMyc, pS2, and WNT1 inducible signaling pathway protein 2, whereas the stimulatory effects of CE on progesterone receptor and amphiregulin expression were weaker than E2. BZA effectively blocked each of these effects and showed no estrogen agonistic effects when used alone. Our results indicate that the stimulatory effects of E2 or CE on breast cancer cells could be completely abrogated by BZA. These studies imply that the CE/BZA, TSEC, exerts antiestrogenic effects on breast cancer cells and might block the growth of occult breast neoplasms in postmenopausal women, resulting in an overall reduction in tumor incidence.


Cancer ◽  
2020 ◽  
Vol 126 (13) ◽  
pp. 2956-2964 ◽  
Author(s):  
Rowan T. Chlebowski ◽  
Aaron K. Aragaki ◽  
Garnet L. Anderson ◽  
Ross L. Prentice

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