The article examines hormonal therapy's role in gynaecological cancers, emphasising its efficacy in hormone receptor-positive tumours and the need for tailored management of menopausal symptoms in cancer survivors, urging further research in this area.

Gynaecological cancers including epithelial and stromal ovarian cancers; endometrial carcinomas; and some gynaecological sarcomas, in particular endometrial stromal sarcomas (ESSs), express estrogen (ER) and/or progesterone (PR) receptors. There is substantial data from numerous case reports, retrospective studies, and small phase 2 studies, about using a variety of hormonal therapies in patients with recurrent /metastatic gynaecological cancers.

This variability almost certainly reflects the heterogeneous populations treated with some studies and reports including patients with hormone receptor-negative tumours and high-grade cancers as well as women with chemotherapy-resistant tumours with a poor performance status where response rates are generally very low.

Although there is data to suggest that women with well-differentiated and/or hormone receptor-positive tumours are more likely to benefit from hormonal therapy, there are conflicting findings regarding the predictors of response in the literature, and very few prospective studies have been performed.

Hormonal therapy is generally better tolerated and, in contrast to chemotherapy, can be administered for prolonged periods with relatively little cumulative toxicity.

We will see the efficacy and potential toxicity of hormonal therapy in each major sub-group.

Ovarian cancers

1. A significant percentage of epithelial ovarian cancers express both ER and/or PR receptors. There is considerable variability in the reported frequency of ER and PR expression in ovarian cancer ranging from 6% to 77% for ER and 26% to 43% for PR.
2. With the treatment data that is available, it seems that the optimal time to consider hormonal treatment is earlier in the disease trajectory such as in asymptomatic patients with CA125 progression and small-volume disease and who have hormone receptor-positive tumours.
3. These patients do not benefit from early initiation of chemotherapy before symptomatic progression, and watchful waiting and inclusion in novel trials using CA125 response or change in doubling time as an endpoint are potential treatment strategies.
4. There may also be a place for hormonal therapy in selected patients with hormone receptor-positive recurrent cancer who have more advanced disease and who have had several lines of chemotherapy, the category in whom disease control with minimal toxicity is particularly important.
5. Granulosa cell tumours of the ovary are also potentially hormonally responsive, with about 30% of granulosa tumours ER-positive and almost 100% PR-positive. Hormonal agents such as progestogens or LHRH agonists have been used widely to treat these patients as they are often elderly and not suitable for aggressive chemotherapy.

Endometrial cancers

They can be subdivided into:

• Type 1 (potentially hormone-responsive)
• Type 2 (hormone-independent) subtypes

Type 1 endometrial cancers are ER-related and are histologically low-grade endometrioid carcinomas. Most of these tumours express either ER and/or PR receptors. The objective response rates range from 15% to 20% with progesterones like Megestrol. Features that predict a better response are hormone receptor expression, low-grade histology, and a long disease-free interval between initial diagnosis and recurrence.

Significant side effects include:

• Weight gain
• Hypertension
• Fluid retention
• Elevated blood sugar
• Sleeplessness
• Tremors
• Thrombosis
• Pulmonary emboli

These can potentially worsen the quality of life and may be life-threatening.

In the uterus, Tamoxifen seems to have a pro-estrogenic effect, promoting disease evolution and hence avoided.

Endometrial stromal sarcomas

Uterine sarcomas (US) are rare mesenchymal malignant tumours, accounting for about 3–7% of all uterine malignancies and less than 1% of all malignancies from the female genital tract. They can be distinguished based on their histology as uterine leiomyosarcoma (uLMS), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromal sarcoma (HGESS), undifferentiated uterine sarcoma (UUS) and other rare types.

A study found that ER and PR were expressed in 53% and 67% of LGESS, 45% and 65% of uLMS, 23% and 31% of HGESS, and 47% and 63% of the overall US, respectively.

Patients with measurable disease and metastatic ESS should be considered for treatment with an aromatase inhibitor. In addition, patients who are at high risk of progression, either following resection of metastases or surgical debulking and have small volume, non-measurable disease should also be considered for treatment with an aromatase inhibitor as an adjuvant treatment.

Cervical cancer

It is not considered a hormonally responsive cancer and estrogen/progesterone receptor positivity has no prognostic significance in this population.

Managing menopausal symptoms in cancer survivors

1. Female patients with cancer may experience premature menopause because of necessary cancer therapeutics or undergo spontaneous menopause by their age. It has been demonstrated that treating symptomatic people improves their quality of life.
2. There is no contraindication for hormone treatment of menopausal symptoms for patients with non-hormonal dependent cancers like cervical or vulvar cancers. For other potentially hormone-dependent cancers discussed above, there are many nonhormonal formulations, and it may be best to offer these first.
3. However, some patients may continue to be symptomatic and discussion of hormone treatment should be undertaken after taking into consideration the patient’s cancer status.
4. It is widely acknowledged that definitive trials are lacking regarding the treatment of hormone-dependent cancers. Given the increase in the female survivor population, management of menopause will require additional study in a timely fashion.

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Bipinesh Sansar, DM Medical Oncology, Associate Professor Medical Oncology at MPMMCC and HBCH, Varanasi.