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Menopausal Symptoms after after Breast Cancer: The Opposing Roles of Pre- and Postmenopausal Estrogens in Obesity-Driven Breast Inflammation and Cancer

Updated: 4 days ago


Preamble:


Ladies, if the following article seems complex, don’t worry. I wrote it to assist women coping with menopausal symptoms after breast cancer.


Recent research has shed light on the crucial role of two types of estrogen in breast cancer risk, especially among women dealing with obesity. Estrone, predominant after menopause, fosters inflammation in breast tissue, potentially supporting cancer growth through interactions between fat cells and cancer cells.


On the other hand, 17β-estradiol, a bio-identical estrogen prevalent before menopause, demonstrates anti-inflammatory properties that may guard against cancer development. Understanding these differences is vital for grasping estrogen’s impact on breast health, offering insights that could lead to innovative strategies for prevention and treatment, particularly for postmenopausal women at higher risk due to obesity.


Introduction

Understanding the impact of menopause and obesity on breast cancer development is crucial for effective prevention and treatment. Recent research highlights the contrasting roles of the major pre- and postmenopausal estrogens, 17β-estradiol and estrone, in driving inflammation and breast cancer growth.


Key Findings


1. Estrogens and Inflammation:


Estrone (Postmenopausal): Predominates after menopause and is pro-inflammatory. It stimulates cytokine production in human mammary adipocytes, particularly when influenced by obesity and cancer. Estrone works with NFκB to induce inflammatory mediators.


17β-Estradiol (Premenopausal): Anti-inflammatory. It opposes the pro-inflammatory actions of estrone, reducing inflammation.


2. Cytokine Expression:


Interaction between adipocytes and cancer cells increases estrone- and NFκB-dependent pro-inflammatory cytokines.

Obesity and menopause drive the expression of cytokines, exacerbating inflammation and potentially promoting cancer development.


3. Gene Induction:


Estrone: Stimulates NFκB-mediated cytokine gene induction through ERα (estrogen receptor alpha).

17β-Estradiol: Counters the gene induction effects of estrone.


4. Experimental Observations:


In obese mice, estrone heightened inflammation while 17β-estradiol alleviated it.

Estrone promoted faster growth of ER+ (estrogen receptor-positive) breast cancer in vivo.


5. Role of HSD17B14:


Converts 17β-estradiol to estrone, associating with poor outcomes in ER+ breast cancer.

High levels of HSD17B14 and estrone drive inflammation, ALDH1 activity, and the formation of tumorspheres.

Reducing HSD17B14 levels or increasing 17β-estradiol can mitigate these effects.


6. Tumor Dynamics:


A high intratumor ratio of estrone to 17β-estradiol increases tumor-initiating stem cells and promotes ER+ cancer growth in vivo.


Conclusion


This study reveals how estrone and 17β-estradiol play opposing roles in breast inflammation and cancer development, especially in the context of obesity and menopause. Estrone’s pro-inflammatory nature and its ability to drive ER+ breast cancer growth highlight the need for targeted strategies to manage inflammation and cancer risk in postmenopausal women. Understanding these mechanisms opens new avenues for prevention and therapeutic interventions aimed at reducing breast cancer incidence and improving outcomes in postmenopausal women.


Menopausal Hormone Therapy Reduces Risk of Colorectal Cancer: Findings from Norwegian Registries

The study aimed to investigate the relationship between menopausal hormone therapy (HT) and colorectal cancer (CRC) risk using Norwegian nationwide registries. Over a median follow-up of 4.8 years involving 466,822 women aged 55-79, it was found that current use of HT, including estrogen therapy (ET) and combined estrogen-progestin therapy (EPT), was associated with a lower risk of CRC overall (RR 0.88; 95% CI 0.80-0.98). Specifically, HT was linked to reduced risks of regionally advanced (RR 0.81; 95% CI 0.70-0.94) and metastatic CRC (RR 0.79; 95% CI 0.62-1.00), but not localised CRC (RR 1.13; 95% CI 0.91-1.41). ET and EPT in oral forms showed similar risk reductions. These findings suggest a protective association between HT use and CRC incidence, particularly in advanced stages. The study supports further exploration of HT’s potential role in CRC prevention and treatment strategies.


For more details, you can refer to the full article here.


References


1. Qureshi, R., Picon-Ruiz, M., Aurrekoetxea-Rodriguez, I., et al. “The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development.” Cell Metabolism, 2020. Link


2. Body identical Estrogen use lowers the risk of colorectal cancer Link

By Dr Purity Carr

GP& Menopause Doctor

Harvey, WA, 6220

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