The association between menopausal hormone therapy and breast cancer remains unsettled,CA: A Cancer Journal for Clinicians

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The association between menopausal hormone therapy and breast cancer remains unsettled
CA: A Cancer Journal for Clinicians ( IF 503.1 ) Pub Date : 2024-05-08 , DOI: 10.3322/caac.21843
Mike Fillon

“Too often, we have patients who are told concretely—by their physicians—that HT therapy is bad—it increases your breast cancer risk; this doesn‘t account for all of the other medical benefits of HRT and quality-of-life factors that impact women during menopause.”

—Ellie Proussaloglou, MD

It has been more than 2 decades since the Women’s Health Initiative (WHI; https://www.whi.org/) alarmed clinicians with a report that found that the combination of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA), when administered to postmenopausal women, increased breast cancer risk as well as the risks for coronary heart disease, stroke, and total mortality without improving quality of life. Since then, several researchers have questioned the findings, and the overarching conclusions have been revisited by WHI investigators themselves. Despite this, clinicians and their patients continue to take on a “safer rather than sorry” stance and often decide against taking the menopausal hormone therapy (HT), regardless of what symptoms may be present.

For example, in a study appearing in the journal Menopause: The Journal of The Menopause Society in April 2023 (doi:10.1097/GME.0000000000002154), WHI investigators conceded that HT yielded considerable benefits. However, they continued to assert that the associated increase in the risk of breast cancer with combined HT (CEE and MPA) remained a valid concern.

In response, a review published in the journal sought to rectify the association between breast cancer and HT—both CEE alone and CEE in combination with MPA, a large source of the misinterpretation (doi:10.1097/GME.0000000000002267). One of the authors, Avrum Z. Bluming, MD, an oncologist at the Keck School of Medicine at the University of Southern California in Los Angeles, explains it this way: “According to WHI’s own data, estrogen alone significantly decreases the risk of breast cancer development (by 23%) and the risk of breast cancer death (by 40%)—crucial information for women who have had hysterectomies.” In addition, “when started within 10 years of a woman’s final period (the ‘window of opportunity’), the WHI now agrees,” says Dr Bluming, that “it significantly decreases the risk for coronary heart disease, improves longevity, is the best and safest treatment for menopausal symptoms, and does not increase the risk of stroke. Further, it decreases the risk of osteoporotic hip fracture, colon cancer, and diabetes mellitus.” The sole issue at play is the association between combined HT (CEE plus MPA) and the risk of breast cancer.

KEY ISSUES

In a new perspective, authors argue that the association between combination hormone therapy (conjugated equine estrogen and medroxyprogesterone acetate) and an increased risk of breast cancer continues to be overstated and, at worst, is incorrect.
Rather than adopting a unilateral opinion that it is universally contraindicated regardless of the symptoms that patients are experiencing, clinicians should consider specific patients and their medical histories when approaching conversations about hormone therapy.

中文翻译：

更年期激素治疗与乳腺癌之间的关系仍不确定

“很多时候，我们的患者被医生具体告知，HT 疗法不好，它会增加患乳腺癌的风险；这并没有考虑到激素替代疗法的所有其他医疗益处以及影响更年期女性的生活质量因素。”

—Ellie Proussaloglou，医学博士

二十多年前，女性健康倡议 (WHI；https://www.whi.org/) 的一份报告令临床医生感到震惊，该报告发现结合马雌激素 (CEE) 和醋酸甲羟孕酮 (MPA) 的组合，当绝经后妇女服用该药物时，会增加患乳腺癌的风险以及冠心病、中风和总死亡率的风险，但不会改善生活质量。此后，一些研究人员对这些发现提出了质疑，WHI 调查人员自己也重新审视了总体结论。尽管如此，临床医生和他们的患者仍然采取“更安全而不是抱歉”的立场，并且经常决定不采取更年期激素疗法（HT），无论可能出现什么症状。

例如，在 2023 年 4 月发表在《更年期：更年期协会杂志》(doi:10.1097/GME.0000000000002154) 杂志上的一项研究中，WHI 研究人员承认 HT 带来了相当大的好处。然而，他们继续断言，联合 HT（CEE 和 MPA）导致的乳腺癌风险增加仍然是一个合理的担忧。

作为回应，该杂志发表的一篇评论试图纠正乳腺癌和 HT 之间的关联——无论是单独的 CEE 还是 CEE 与 MPA 的结合，这是误解的一个重要来源 (doi:10.1097/GME.0000000000002267)。其中一位作者、洛杉矶南加州大学凯克医学院的肿瘤学家 Avrum Z. Bluming 医学博士这样解释道：“根据 WHI 自己的数据，单独使用雌激素就可以显着降低乳腺癌的风险。”癌症发展（23%）和乳腺癌死亡风险（40%）——对于接受子宫切除术的女性来说至关重要的信息。”此外，“WHI 现在同意，在女性末次月经（‘机会之窗’）后 10 年内开始服用，”布卢明博士说，“它可以显着降低患冠心病的风险，延长寿命，是针对更年期症状的最佳和最安全的治疗方法，并且不会增加中风的风险。此外，它还能降低骨质疏松性髋部骨折、结肠癌和糖尿病的风险。”唯一的问题是联合 HT（CEE 加 MPA）与乳腺癌风险之间的关联。