Summary

Experts agreed that while chemotherapy is an effective first-line treatment for HR-positive MBC, endocrine therapy should be considered over chemotherapy for patients who are not in visceral crisis.

The efficacy demonstrated by hormonal therapy in treating hormone receptor-positive metastatic breast cancer has changed the landscape of treatment. This consensus recommendation was prepared to educate the community oncologists regarding the optimal use of hormonal therapy in hormone receptor positive metastatic breast cancer (HR+ mBC).

Breast cancer (BC) is a major health issue and one of the common types of cancers with an increasing incidence rate both globally and within India. The last few years have witnessed tremendous advances been made in the discovery of new breast cancer drugs. Improved understanding of the biologic heterogeneity of BC has also led to more effective and individualised approach to treatment.

The demonstrated efficacy of hormonal therapy in treating hormone receptor-positive metastatic BC (MBC) has changed the landscape of treatment by providing a well-tolerated alternative to surgical oophorectomy and chemotherapy.

Estrogen receptors (ERs) and progesterone receptors (PRs) are found positive in about 20–45% of Indian breast cancer patients. Although metastatic breast cancer is unlikely to be cured, there have been meaningful improvements in survival due to the availability of more effective systemic therapies such as endocrine therapy in the treatment of hormone-sensitive disease.

Advancements made in the field of metastatic breast cancer mandates that treatment algorithms and guidelines be updated accordingly so that patients may be offered most effective and least toxic therapeutic options based on breakthrough clinical trials data.

These consensus recommendations were prepared by expert oncologists from all over India to educate the community oncologists regarding the optimal use of hormonal therapy in hormone receptor-positive MBC.

Surgery of the primary tumour in hormone receptor-positive metastatic breast cancer patients

Surgery of the primary tumour is an invasive approach and is often associated with adverse outcomes. Primary tumour removal can induce an angiogenic surge, which, in turn, can promote further metastases. Surgery of the primary can also lead to the release of growth factors related to surgical wounding. Immune suppression caused by the surgical procedure and anaesthesia are some other problems associated with locoregional treatment.

Further, there is a lack of sufficient clinical data which demonstrates improved outcomes with surgery. A Turkish Study, published in the Journal of Clinical Oncology in 2017, showed that locoregional therapy along with systemic therapy may prolong survival in subsets of patients with ER+ disease and solitary bone metastasis. But these results were based on exploratory analyses.

As per the experts, modern systemic therapy has contributed to improved survival in patients with distant metastasis.

1. The panel concluded that as substantial evidence is not present for locoregional treatment to replace systemic treatment as the standard of care in patients with HR-positive MBC; upfront locoregional control is currently not recommended.
2. They further added that if locoregional therapy should be considered, it should be individualised as per the age of the patient, the ER status, sites of metastatic disease and the response to therapy.

Treatment options in hormone receptor-positive metastatic breast cancer patients

The expert consensus was that endocrine therapy rather than chemotherapy should be offered in patients with HR-positive MBC who are not in a visceral crisis.

First line hormonal therapy after ovarian ablation for premenopausal women

Ovarian ablation by oophorectomy, ovarian radiation, or hormonal suppression comprises the initial strategy for treatment of HR-positive MBC in premenopausal women. Ovarian ablation combined with aromatase inhibitors (AIs) is now viewed as an effective therapeutic option in premenopausal women.

1. The expert panel recommends the combination of AIs and palbociclib, as the first line hormonal therapy after ovarian ablation.
2. If palbociclib treatment is not workable, the panel recommends the use of AIs.
3. The use of fulvestrant is recommended in patients with bone only disease. However, the cost factors and mode of administration (intra muscular administration in every month) are major factors which can affect patient’s adherence with fulvestrant.

Role of ESR1 Mutation Testing

ESR1 is the gene that encodes the estrogen receptor (ER). Mutations of the ESR1 gene- ligand-binding domain (LBD) mutations, gene amplification, or an ESR1/YAP1 translocation, are potential mechanisms of resistance to ET. Assessing the presence of ESR1 mutations in MBC patients can thus, help in individualising treatment for MBC patients.

The panel opined that the current evidence on ESR1 mutations needs prospective studies in which patients are randomised and treated according to the ESR1 mutation status. The potential use of ESR1 mutation status as a predictive biomarker to guide the choice of the optimal therapeutic strategy needs further development; hence, at present, the panel does not recommend testing for ESR1 in routine clinical practice.

Second Line Hormonal Therapy

For patients who have received aromatase inhibitors previously, the experts recommend a combination of fulvestrant and palbociclib. As an alternative, the combination of everolimus and exemestane is also recommended, however, it is important to be aware of its side effects. The oncologist needs to consider the risk to benefit ratio before prescribing the combination.