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.
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 oestrogen receptor positive (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 in The Lancet article, 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).
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 (historical questioning) 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.
Panel discussion on Breast Cancer, Menopause and HRT
Leading clinicians collaborate in an in-depth panel discussion, on the link between Breast Cancer, Menopause and HRT.
HRT and Breast Cancer – What you need to know
The mere mention of HRT can spark fears of breast cancer, but should it? Breast surgeon Professor Zoe Winters and Consultant Gynaecologist Jeannie Yoon set the record straight.
