Long-Term Endocrine Therapy and Metastatic Breast Cancer

Introduction

Endocrine therapy (ET) is one of the commonly used procedures for the treatment of breast cancer that has metastasized (spread to different parts of the body from the breast). The most prevalent cancer reported in females is breast cancer. Twenty-five percent of women with metastatic breast cancer usually have a five-year survival rate, as per the research. This article further discusses the details of endocrine therapy for breast cancer, the agents used, and its long-term impact on metastatic breast cancer.

Prevalence of Breast Cancer

Breast cancer is the second most common cancer affecting the population on a global scale. According to data from the WHO (World Health Organization), more than 6,70,000 deaths in 2022 were due to breast cancer worldwide. The prevalence rate of breast cancer is around 13 to 16 percent of all female cancers.

What Is Endocrine Therapy?

ET, or hormonal therapy, has a vital role in the management of metastatic breast cancer, particularly for patients detected with HR+ve (human receptor positive). Certain hormones like estrogen initiate the growth of the cancer, which can be inhibited by targeted endocrine therapies. Endocrine therapy is effective in 70 percent of the cases detected with HR+ve metastatic breast cancer, according to the research reports.

Agents Used in the Endocrine Therapy

There are multiple agents used in endocrine therapies that have shown improvement in cases of survival rates of metastatic breast cancer and reduction in recurrence rates, such as:

• Selective Estrogen Receptor Modulators (SERMs):

1. Aromatase inhibitors (AIs) which include Letrozole, Exemestane, and Anastrozole.

2. Tamoxifen

What Are the Complications Associated with Endocrine Therapy?

The agents used in endocrine therapy have benefits, but they also have certain side effects, such as:

• Stroke.

• Formation of blood clots in the lungs and lower extremities.

• Depression.

• Mood swings.

• Bone loss (mostly seen in females).

• Pain in the joints.

• Hot flashes.

• Loss of appetite.

• Weight loss.

• Difficulty breathing.

• Angina (chest pain).

What Are the Long-Term Benefits of Endocrine Therapy for Metastatic Breast Cancer?

Several long-term benefits of endocrine therapy for metastatic breast cancer (MBC) are:

• Around two out of three cases of metastatic breast cancer are detected as HR-positive. The cells of MBC contain proteins that continue to grow and spread cancer. Many patients diagnosed with HR-positive MBC have been shown to benefit from hormonal or endocrine therapy, which stops these cells from spreading cancer further by restricting its growth. Endocrine therapy also observes a prolonged control of the disease period.

• According to clinical trials, hormonal therapy in combination with agents such as CDK 4 (cyclin-dependent kinase) or CDK 6 inhibitors can extend disease-free survival rates. This is crucial in the healthcare setting, where the main goal of treatment is to control the disease while maintaining patients' QoL (quality of life).

• When compared to the conventional chemotherapy method, endocrine therapy is less toxic, making it a preferred method for long-term management of patients with metastatic breast cancer.

• Endocrine therapies can be performed in patients with MBC for a long time without much-deteriorating side effects when compared with chemotherapy procedures.

When Is Endocrine Therapy Indicated for Breast Cancer?

Endocrine or hormonal therapy is indicated during the following:

• Adjuvant Therapy (After Surgery): Endocrine therapy is generally used after the surgical procedure to minimize the risk of recurrence of breast cancer.

• Neoadjuvant Therapy (Before Surgery): Endocrine therapy may also be used before surgical therapy (neoadjuvant therapy) in a few instances, mostly in cases of large tumors.

• Continued Therapy Till Five Years: In patients suspected of having a higher risk of recurrence, as detected or evaluated based on the Breast Cancer Index (a test used to predict the chances of recurrence of early-stage breast cancers), an endocrine therapy of more than five years is provided.

What Is the Schedule for Endocrine Therapy After Breast Cancer Surgery?

After the surgery for breast cancer, endocrine therapy is usually necessary to prevent the risk of recurrence of cancer. According to study reports, consumption of a combination of agents such as Aromatase inhibitors (AI) drugs with Tamoxifen is proven to be more effective than the use of Tamoxifen alone for five years.

Schedule for Endocrine Therapy (For Postmenopausal Women)

• Tamoxifen (2 years) followed by AI for 2 to 3 years (total of five years of therapy).

• Tamoxifen (2 to 3 years) followed by AI for five years (total 7 to 8 years of endocrine therapy).

• Tamoxifen alone for 5 to 10 years (a preferred option in patients who are unable to take aromatase inhibitors alone).

• Aromatase inhibitors are given alone for 5 to 10 years.

• AI for two years, followed by three years of Tamoxifen (five years of hormonal therapy).

Schedule for Endocrine Therapy (For Premenopausal Women)

• Tamoxifen alone for 5 to 10 years (without or with ovarian suppression).

• Tamoxifen (5 years) followed by five years of Aromatase inhibitors for patients going through menopause (without or with ovarian suppression).

• Aromatase inhibitors in combination with some ovarian suppression using a drug called LHRH (luteinizing-hormone releasing hormone) for 5 to 10 years.

Women with a heightened risk of recurrence of cancer as per the breast cancer index are usually provided with more than five years of endocrine therapy as per suggestion from healthcare professionals. Tamoxifen for ten years is comparatively more effective than taking it for five years. The schedule for hormonal therapy may vary based on different cases, so It is advised to discuss the therapy schedule with the healthcare professionals.

Conclusion

Endocrine or hormonal therapy remains the mainstay of the treatment for patients diagnosed with metastatic breast cancer. Endocrine therapy, in combination with a few targeted agents such as CDK4 and CDK6, has shown improved clinical outcomes in patients with metastatic breast cancer. With the ongoing research, combining endocrine therapy with different novel targeted agents and immunotherapy should continue to bring new hopes and advancements in medical oncology. These current or upcoming combinations of endocrine therapies may improve clinical outcomes and provide a better QoL to patients diagnosed with metastatic breast cancer.