More than 80% of breast cancers are due to lifestyle factors in the context of increasing age, clinical factors, and one’s individual population genetics which makes each one of us “different”, and is a consequence of multiple small changes in one’s DNA after birth.
We all experience a natural and progressive reduction in our circulating female sex hormones: oestrogen, progesterone and proportionate levels of androgens or male hormones. Progesterone levels are the first to decline at approximately 35 years of age. Our levels of oestrogen decline later around 45 to early 50s in the majority of women.
Our female sex hormones are constantly changing within our body secondary to reproductive factors (age of menarche; age of first live birth, number of children and duration of breastfeeding). These inherent levels of natural hormones (called endogenous) within each woman may be affected by adding hormones
(called exogenous) such as oral contraceptives and HRT.
Other lifestyle factors are likely to act through hormones such as: adiposity (amounts of body fat) and alcohol consumption. One’s physical activity is also an important modifiable risk factor.
Endogenous (inherent individual) hormone levels are influenced by childbearing, which reduces breast cancer risk by 7% per birth. Breast feeding further reduces breast cancer risks by 4% per year of breastfeeding.
Exogenous (external addition) hormones such as oral contraceptives administered over 15 years at various ages have a very small increase in breast cancer risk that is greatly outweighed by a corresponding reduction in uterine and ovarian cancer, so that the net effect on female cancers is beneficial.
In a recent meta-analysis of 13 cohort studies in women under 55 years of age (median age 42 years) assessed over 8 years; 2% developed young onset breast cancer. 15% reported using hormone therapy; 6% used combined oestrogen and progesterone; 5% unopposed oestrogen. 4% of non-users developed breast cancer Lancet Oncology; 2025
Hormone therapy was not linked to incident breast cancer risk under 55 years of age. However, combined oestrogen (E) and progesterone (P), and use for more than 2 years, increased breast cancer risks (18%). This means an 18% higher risk of breast cancer occurring at any time point, compared to E only users or non-users. Combined E and P were associated with oestrogen negative (ER-) breast cancers, and triple negative cancers.
Ovarian function ceases with menopause; thereafter oestrogen levels fall substantially and progesterone levels fall to near zero. Endogenous oestrogen synthesis in postmenopausal women occurs mainly in adipose/fatty tissue, catalysed by the enzyme aromatase. Postmenopausal oestrogen levels therefore correlate strongly with the amount of adipose tissue, and hence body mass index (BMI). Postmenopausal oestrogen is a strong determinant of ER+ breast cancer, whereby the latter accounts for three quarters of all breast cancer cases and deaths.
In a meta-analysis of all studies on the duration and types of menopausal HRT used, and breast cancer risk www.thelancet.com, the authors conclude that there are excess breast cancer risks in women from 50-69 years of age, for women using HRT for 10 years and longer, starting at 50 years. This pertains largely to combination HRT (oestrogen and progesterone). The risk in these groups varies from 1 cancer in 25 users (continuous combined progesterone), to 1 cancer in 30 users (intermittent/cyclic combined progesterone). The risks are significantly lower in women taking oestrogen only (permissible only in those without a uterus, following a hysterectomy) where the risk is 1 extra cancer in 100 users. These risks persist up to 10 years in past users, after stopping HRT.
The above risks pertain to greater risks of: invasive cancers compared to never users; current HRT users; and persist up to 10 years after stopping HRT. The excess risks are greater for oestrogen receptor positive (ER+) cancers than for oestrogen receptor negative (ER-) disease. The risks are also greater for invasive lobular cancers compared to invasive ductal cancers. The breast cancer risks vary according to BMI, where increases in perimenopausal BMI are associated with increases in breast cancer risks in never users of HRT, that persists across all ages. The risks associated with increasing BMI are not seen amongst current users of HRT, as adiposity attenuates the excess risk of HRT. In obese women, the use of oestrogen-only HRT adds little to the adiposity-associated stimulation of their breast tissue. However, the risks are higher in lean women who are current users of oestrogen only HRT. Lean and obese women have similar absolute increased risk with the addition of progesterone.
Summary of this meta-analysis: For women of average weight in developed countries, 5 years of HRT use starting at 50 years of age would cause an appreciable increase in the probability of developing breast cancer at ages 50-69 years.
However, it is important to note that the study is based on 24 prospective studies comprising three quarters of postmenopausal women (number = 108,647) that were diagnosed with invasive breast cancer at 65 years (mean age) in 2005 (median year). The 34 retrospective studies comprised a quarter of women (number = 35,240) diagnosed with invasive cancer in 1995.
Current protagonists of HRT for menopausal symptoms and quality of life benefits discuss the fact that previous HRT preparations were synthetic, as opposed to being body- and bio-identical. There were likely issues of recall for women in retrospective studies, or in general relating to past use, and duration of use.
So called “modern” HRT is underpinned by our understanding of the overall health and quality of life benefits of replacing oestrogen. I refer to this as the “queen of hormones” with reductions in: cardiovascular (heart) disease, dementia, abdominal obesity, and overall breast cancer mortality (deaths related to breast cancer). Oestrogen replacement alone does not increase breast cancer risks compared to the average population risks that are multifactorial in all women (breast cancer risk prediction tools). It is the addition of progesterone, or combined (oestrogen and progesterone) HRT that raises these risks. It is unclear why oestrogen-progesterone preparations would have a greater effect than oestrogen-only HRT.
In principle, modern HRT should comprise bio-identical oestrogen that is ideally administered through the skin as a gel or patch. The majority of women with an intact uterus require progesterone to stop the unopposed stimulation of oestrogen acting on the uterine lining to produce thickening thereof and breakthrough bleeding. Likewise, bio-identical progesterone is advised and should be used in the lowest doses in a sequential manner that is recommended by your menopause specialist or consultant gynaecologist. This may entail a combined oestrogen and progesterone skin patch, intra-uterine progesterone (Mirena coil), or an oral progesterone tablet called Utrogestan. Utrogestan contains micronized natural progesterone (called body-identical). It is derived from plants such as yam and soy, and is chemically identical to progesterone produced by the ovaries.
Current recommendations are to use bio-and body-identical HRT, and to consider type of administration in the context of individual breast cancer risk (breast cancer risk assessment tools). This is underpinned by contemporary breast screening individualised to mammographic breast tissue density and bespoke frequency of breast screening.
Breast cancer risks
There are a number of validated breast cancer risk assessment tools that can be referred to in Professor Zoe Winters’ blog on Young Onset Breast Cancer 13/06/2025:
These algorithms are validated tools developed to assess the risks of carrying a BRCA 1 or 2 mutation, and of developing breast and ovarian cancer such as: BOADICEA/CanRisk or IBIS. They incorporate genetic results, family history, polygenic risk scores, clinical and lifestyle factors and hormonal data.
Women at high risk of developing breast cancer (estimated lifetime risk of 20% or more) may still consider HRT. However, each woman needs to understand the associated risks in the context of the Lancet 2019 meta-analysis, and the use of “modern” HRT that is carefully managed between their consultant breast and menopause specialist, and their geneticist.
The risk assessment tool that I currently use is called the Breast Cancer Surveillance Consortium Risk Calculator that helps categorise women into low, intermediate and high risk, without integrating genetic testing. This guides my recommendations regarding breast screening, in terms of age of starting, and frequency intervals. Every woman undergoing a mammogram should know their breast tissue density, where dense breasts require additional imaging that includes IV contrast: either using a contrast enhanced mammogram (CE-M), or an abbreviated breast MRI This is based on the latest findings of the UK BRAID randomised trial featured in the Daily Mail 01/06/25.
Lifestyle factors
Body mass index (BMI): A BMI of 25 – 29 at 60 years of age increases breast cancer risks by 20% compared to a BMI under 25. This is also associated with increases in ER+ breast cancers compared to ER- cancers.
Alcohol: Consuming more than 10g of alcohol per day increases risks of breast cancer that are equivalent to taking oestrogen only HRT, or 1 cancer per 100 women before 75 years of age. These are typically ER+ breast cancers.
Breast tissue density: BRAID trial
Both these lifestyle factors are integrated into the CanRisk risk assessment tool, including the mammographic assessment of breast tissue density.
References:
- Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 2019; 394: 1159-1168.
- London Breast Health blog on Young Onset Breast Cancer, 13/06/2025
- Hormone therapy use and young-onset breast cancer: a pooled analysis of prospective cohorts included in the Premenopausal Breast Cancer Collaborative Group. Lancet Oncology 2025; 26: 911-23
- Comparison of supplemental breast cancer imaging techniques—interim results from the BRAID randomised controlled trial. Lancet 2025; 405 (10493): 1935-1944