Key considerations for assessing suitability, balancing benefits and risks, and individualising care…

Treating menopausal symptoms in women with a history of cancer, or those at increased risk, remains a clinical challenge. While menopausal hormone therapy (MHT) is the most effective option for symptom management, its use in this group requires careful, individualised assessment. Appropriateness depends on factors such as cancer type, hormone receptor status, and individual risk profile. Balancing symptom relief with recurrence or progression risk involves a clear understanding of the impact of MHT in different cancer contexts, including after risk-reducing surgery.

Assessing breast cancer risk and MHT use

Breast cancer is the most common cancer encountered when managing menopause, with around one in seven Australian women diagnosed in their lifetime. When considering MHT, understanding a patient’s personal baseline risk of breast cancer is an important first step in guiding treatment decisions.

Risk can be broadly categorised into three levels:

• Average or slightly increased risk (1.5 times the average population), applying to around 95% of women
• Moderately increased risk (1.5–3 times the average population), accounting for <4% of women
• High risk (>3 times the average population), seen in <1% of women

These categories are influenced by a wide range of factors, including three modifiable lifestyle factors: physical activity, diet, and weight. Encouraging patients to complete a structured risk assessment can offer personalised insights and help support shared, evidence-based decision-making about MHT.

Useful tools for breast cancer risk assessment

The iPrevent tool, developed by Peter MacCallum Cancer Centre and endorsed by Cancer Council Australia, offers the most comprehensive risk assessment available to Australian women. This free online tool requires approximately 30 minutes to complete and provides both 10-year and lifetime risk calculations compared to age-matched averages.

Alternative tools include the Tyrer-Cuzick model (formerly IBIS) from the UK and the Gail model from the United States. While the Gail model is quicker to complete, it provides less detailed analysis than iPrevent.

MHT recommendations based on breast cancer risk levels

For women with average, slightly increased, or moderately increased risk of breast cancer, MHT remains an appropriate option for managing menopausal symptoms. For women with high risk of breast cancer, MHT is generally not recommended.

Importantly, the increase in breast cancer risk associated with MHT is small. With combined oestrogen and progestogen therapy, the risk is less than one extra case per 1,000 women per year and only appears after five years of use. Oestrogen-only MHT does not increase breast cancer risk, and there is no increase in breast cancer mortality associated with MHT use.

Risk-reducing surgery and the role of MHT

Although MHT is generally not recommended for women at high risk of breast cancer, it is an important option for those who have undergone risk-reducing surgery and should be considered in this context.

For women with a very high lifetime risk of breast or ovarian cancer, risk-reducing surgery (involving removal of the ovaries, fallopian tubes, and sometimes the uterus) is often advised. While effective at reducing cancer risk, it can induce premature menopause subsequently increasing the risk of cardiovascular disease, osteoporosis, cognitive decline, and a reduction in quality of life. In these cases, MHT is often not just appropriate but necessary.

Several studies have shown that MHT following risk-reducing surgery does not increase breast cancer risk and may even reduce it.^1-4 Current guidelines support the use of MHT up to the average age of natural menopause, at the lowest effective dose, to protect long-term health and quality of life.

Using MHT after breast cancer

For women with a history of breast cancer, the general recommendation is to avoid MHT, regardless of hormone receptor status. While this may seem counterintuitive in cases of receptor-negative disease, the evidence remains uncertain.

Four prospective observational studies have shown no increase in recurrence among women using MHT for up to 10 years.^5-8 Four prospective observational studies have shown no increase in recurrence among women using MHT for up to 10 years.^5-8 In contrast, RCTs are more cautionary. Of the four major randomised controlled trials, two showed a significant increase in breast cancer recurrence with MHT, particularly in women with oestrogen receptor–positive disease; one reported a non-significant increase, and a small trial of oestrogen-only therapy in women with receptor-negative disease found no increase. ^9-12 Based on this, guidance advises against the use of MHT in this population.

Despite general recommendations against MHT use in this population, there are people who experience debilitating menopausal symptoms that do not respond to non-hormonal therapies. Therefore, some women may choose to use MHT regardless of the associated risks. In such cases, a shared decision-making approach is essential, including written information about the risks and benefits, and clear documentation of informed consent.

Ovarian cancer risk and MHT

Evidence on the risk of ovarian cancer with MHT is mixed, but overall the risk is considered low and not a major factor in treatment decisions. A 2015 meta-analysis found a small increase in serous and endometrioid cancers, translating to two extra cases per 10,000 women per year.¹³ More recent studies from the E3N cohort and the Women’s Health Initiative (WHI) suggest that most combined oestrogen–progestogen regimens do not increase ovarian cancer risk; however, E3N observed a modest increase specifically with oestrogen plus progesterone or dydrogesterone. For oestrogen-only therapy, WHI reported a higher risk whereas E3N found no significant increase.^14,15

Using MHT after ovarian cancer

When managing menopausal symptoms in women with a history of ovarian cancer, treatment decisions depend on cancer type.

For most people with epithelial ovarian cancer (90% of all ovarian cancers), evidence from a Cochrane review and a 2023 meta-analysis suggests that MHT does not worsen outcomes.^16,17 However, MHT is not recommended for women with low-grade serous ovarian cancer due to frequent hormone receptor positivity, nor for those with sex cord stromal tumours due to limited data.

In contrast, MHT is considered appropriate for younger women with germ cell tumours, given their favourable prognosis. Due to the differing outcomes associated with ovarian cancer subtypes, it is essential to confirm the specific tumour type and hormone receptor status, and to consult the treating oncologist before initiating MHT.

MHT and endometrial, cervical, vulval, vaginal cancers

In endometrial cancer, the appropriateness of MHT depends on tumour type, stage, and extent of surgical treatment.

In women with early-stage disease who have undergone hysterectomy and bilateral salpingo-oophorectomy, MHT has not been shown to increase recurrence. This is supported by a prospective study and a Cochrane review showing no increased risk with oestrogen-only therapy.^18,19 Some oncologists may still prefer combined therapy depending on tumour characteristics. MHT should be individualised based on patient preferences and tumour profile. However, it is not recommended for advanced disease or non–hormone-dependent subtypes (e.g. sarcoma, serous, or clear cell carcinoma) due to insufficient safety data.

MHT is considered appropriate for symptom relief in women treated for cervical (squamous and adenocarcinoma), vaginal, or vulvar cancer. Cervical cancers are not hormone-responsive, and both a 2021 systematic review and a case-control study found no increased risk of recurrence or reduced survival with MHT.^20,21 Similar evidence supports its use in vaginal and vulvar cancers, which are also typically hormone independent.

MHT and other cancer

MHT is appropriate for symptom relief in women with a history of colorectal or haematological cancer. Observational studies and randomised trials have shown no increased risk in colorectal cancer, with some evidence that combined oestrogen and progestogen therapy may reduce risk.^22-24

For lung cancer, data are limited and there is no clear consensus. If symptoms are severe and non-hormonal options are ineffective, MHT may be considered cautiously on a case-by-case basis.

In malignant melanoma, studies suggest either no effect or a slight increase in risk with oestrogen-only MHT.^25,26 In such cases, low-dose continuous combined therapy may be an option for symptom relief, but decisions should be made individually based on symptom severity and lack of alternatives.

Key points

• MHT is appropriate for women at average or moderate breast cancer risk, following individual assessment.
• Generally, MHT should be avoided after breast cancer, but can be considered in rare cases with informed consent.
• Offer MHT to women undergoing risk-reducing surgery before menopause, until the average age of menopause.
• Use MHT cautiously in those with gynaecological cancers—it is appropriate after early-stage endometrial and most ovarian cancers, but avoid in hormone-sensitive or advanced subtypes.
• MHT is acceptable for symptom relief in non–hormone-dependent cancers, including cervical, vaginal, vulval, colorectal, and haematological cancers.

References

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