Menstrual Cycle and Breast Cancer Risk
The year 2020 saw around 2.3 million women being diagnosed with breast cancer. As per the latest report from GLOBOCAN published in February 2021, breast cancer has surpassed lung cancer in being the most prevalent cancer type in the world.
Compared to the high risk of breast cancer in women, the risk of breast cancer in men is a minuscule 0.5-1%. A significant reason for the high risk and prevalence of breast cancer in women is attributed to the reproductive hormone, i.e., estrogen and progesterone fluctuations.
To understand the relationship between the menstrual cycle and breast cancer risk, we must know that the most common breast cancers are hormone receptor-positive breast cancers - the cancer cells have estrogen or progesterone or both types of receptors.
These breast cancer cells grow and multiply when exposed to estrogen and progesterone. However, a few types of breast cancer are hormone-receptor negative, which means that these breast cancer cells have no hormone receptor cells and are often more challenging to treat.
Every girl who begins her menstrual cycle has a 5% risk of developing breast cancer in her lifetime. This is because the mammary glands begin forming and remain under the influence of different reproductive hormones as soon as a girl hits puberty, during pregnancy, and even during lactation.
The constant fluctuations in estrogen and progesterone levels during a woman’s reproductive life affect the mammary gland function, cell growth, turnover, and immune cells like the regulatory T cells and the macrophages.
Together, these effects cause increased instability of the individual’s genome, increase their susceptibility to genetic mutations, reduce their immunity, and trigger breast cancer development.
Menopause and Breast Cancer Risk
Menopause does not cause breast cancer, but the risk of developing breast cancer increases as the woman ages. According to statistics, a woman who attains menopause after 55 years of age has an increased risk of breast, ovarian, and uterine cancers.
This risk is also greater if a woman starts menstruating before the age of 12 years. Therefore, the longer a woman’s reproductive life, the longer her breast tissue is exposed to hormonal fluctuations, increasing her risk for breast cancer.
It has been observed that postmenopausal women have a lower risk of breast cancer compared to premenopausal women of the same age and with the same childbearing pattern. Also, the risk of breast cancer increases by 3% for each year that menopause gets delayed.
So, women who attained menopause later than 55 years of age had a 30% increased risk of breast cancer than women who reached menopause at 45 years of age.
Postmenopausal breast cancer is known to be less aggressive than breast cancer that occurs in younger women. However, obesity or increased weight is an independent risk factor for breast cancer in menopausal women. This is because serum estradiol (a form of the female hormones estrogen) is increased in obese patients, triggering breast cancer development.
Another study re-iterated the findings mentioned above, stating that lower age of menopause had a protective effect and reduced breast cancer risk compared to the higher age of the woman. This protective effect may be more substantial in leaner women.
Many women take combined hormone therapy to relieve menopausal symptoms like hot flashes and osteoporosis. This treatment is also called Hormone Replacement Therapy (HRT).
In this therapy, estrogen and progesterone are combined and administered to postmenopausal women to help manage their symptoms.
However, HRT increases a woman’s risk of developing breast cancer, stroke, heart attack, and blood clots.
How Genes Influence Postmenopausal Breast Cancer Risk
Genetics plays a significant role in the development of breast cancers. Around 5% to 10% of breast cancers occur when an abnormal gene is passed from the parent to the child.
The most commonly inherited genes that lead to breast cancer are the BRCA1 and BRCA2 genes. However, genes that influence the risk of breast cancer in postmenopausal women include- ESR1, PGR, XRCC1, VDR, CAT, CYP2C19, and XRCC3, among others.
ESR1 Gene
ESR1 or the Estrogen Receptor 1 gene provides instructions for the production of estrogen receptor production and ligand-activated transcription factor. These estrogen receptors play a role in growth, development, sexual development, and reproductive functions. Unfortunately, they also play a vital role in breast cancer development, endometrial cancer, and osteoporosis.
rs9340799 is a Single Nucleotide Polymorphism (SNP) in the ESR1 gene and located on chromosome 6. A study on Mexican women showed that women carrying the XbaI (WT/G or G/G) ESR1 genotype have a 12.26 times greater risk of developing postmenopausal breast cancer than those carrying the WT/WT genotype.
However, women with t or the wild type of XbaI had no association with breast cancer. Also, postmenopausal women who were both heterozygous and homozygous for XbaI had a strong association with breast cancer.
PGR Gene
PGR or Progesterone Receptor gene mediates the physiological effects of the hormone progesterone, which plays a vital role in the reproductive cycle in women.
rs10895068 is an SNP in the PGR gene, which is located on chromosome 11. Having two AA alleles or at least one A allele increases the risk of breast cancer in postmenopausal women by 2.5 times compared to those with the GG genotype.
Recommendations To Reduce Post-Menopausal Breast Cancer Risk
Lifestyle changes can help reduce the risk of breast cancer in postmenopausal women.
- Maintaining a healthy weight
Gaining weight after menopause can increase a woman’s risk for breast cancer. One must maintain a healthy weight throughout their life to reduce the risk of cancer (According to The American Cancer Society)
- Limiting or avoiding alcohol consumption
Though the direct link between alcohol consumption and increased risk for breast cancer has not been established yet, consuming even lower amounts of alcohol can increase your risk for breast cancer.
- Breastfeeding for longer
Studies have shown that the longer a woman breastfeeds, the lower her risk for breast cancer. For example, researchers have found that for every 12 months that a woman breastfeeds, her risk for breast cancer decreased by 4.3%
- Reducing HRT or post-menopausal hormonal therapy
Women who opt for hormonal therapy after menopause must speak with their doctor as these therapies increase the risk for breast cancer. Ask for non-hormonal alternatives or short-term hormone therapy options to manage menopausal symptoms.
- Following a healthy diet
Following a healthy diet low on red meat, processed foods, sugary foods, and fat can reduce your risk for breast cancer. However, the association between diet and breast cancer is still under research.
- Quit smoking
Smoking increases the risk for all types of cancer, including breast cancer. Therefore, women who are smokers must quit the habit to lower their risk of developing breast cancer post-menopause.
- Opt for genetic Counselling
It is recommended that women with a familial history of breast cancer undergo genetic counseling. This can help determine the course of action to reduce their risk and chances of developing breast cancer.
- Regular monitoring
Routine doctor visits and breast exams are recommended for all women above the age of 35 years. Regular monitoring reduces the chances of late detection and improves prognosis.
Summary
- Breast cancer risk is strongly linked to a woman’s menstrual cycle. This increased risk is because of reproductive hormones estrogen and progesterone, both of which contribute to breast cancer risk. Menopause does not cause cancer, but the risk of breast cancer development increases as a woman ages. However, postmenopausal breast cancers are less aggressive than premenopausal breast cancers.
- Women who take hormonal therapy after reaching menopause are at a heightened risk of breast cancer.
- Breast cancer has a strong genetic link, and women with a familial history of the condition are at a high risk of developing it. In addition, some SNPs in genes like the ESR1, XRCC1, PGR, etc., are known to increase breast cancer risk in postmenopausal women.
- Making lifestyle changes, including eating a healthy diet, staying physically active, being cautious about hormone replacement therapy, and opting for genetic counseling, can help reduce a woman’s risk of breast cancer and encourage early detection.
References:
- https://www.who.int/news-room/fact-sheets/detail/breast-cancer
- https://www.frontiersin.org/articles/10.3389/fonc.2016.00267/full
- https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-hormone-receptor-status.html
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078652/
- https://iv.iiarjournals.org/content/33/2/483
- https://pubmed.ncbi.nlm.nih.gov/10517172/
