Targeted Breast Cancer Therapies: New Challenges To Fight Against Resistance

All about targeted drugs and breast cancer by Oncologist Dr S Jayanthi.

Breast Cancer Awareness Month 2022: Breast cancer in Indian women is seen a decade earlier, and Triple Negative Breast Cancer (TNBC), an aggressive variant of breast cancer, constitutes a significant proportion. This subtype is usually associated with an unfavourable prognosis and is characterized by a higher incidence rate among younger women, aggressive tumour behaviour and early recurrence. Therefore, the treatment outcomes are different when compared to the western world. However, one size fits all is a myth, especially regarding cancer treatment and management. All about targeted drugs and breast cancer by Dr S Jayanthi, Senior Consultant Medical Oncologist, American Oncology Institute, LB Nagar Hyderabad.

Treating Breast Cancer

The primary goal in treating breast cancer is to control the disease to achieve a cure. However, the other desirable outcomes of treatment are to improve survival rates, minimize the risk of distant metastases and local recurrence, cosmesis, relief of symptoms, and offer a quality life. Different treatment modalities include surgery, radiotherapy, systemic therapy such as hormonal manipulation, and treatment targeted at the human epidermal growth factor receptor 2 (HER2) protein.

Targeted Therapy Drugs

As the name suggests, targeted therapy uses medicines that destroy cancer cells or slow their growth. The last decade has opened doors for new treatment avenues and improved patient survival.

• Like chemotherapy, targeted therapy drugs are helpful against cancers, especially the ones that spread to distant body parts. The evolution of personalized medicine or precision medicine has broken the myth that all breast cancers should be treated alike because breast cancer is not a single disease. So what is precision oncology? It's a treatment suited for a specific cancer type because it differs in different people. The same stage and the same disease will behave differently in two people.
• Targeted therapies can do other things to the cancer cells they target. For example, they can prevent them from living longer than usual or destroy and kill cancer cells. Meanwhile, the recent advances and breakthroughs in molecular oncology have further revolutionized cancer care and opened new treatment options. Targeted therapies directed against specific aberrations have helped in saving uncountable lives.

Targeted Drugs And Breast Cancer

Nearly 20% to 25% of breast cancers have a human epidermal growth factor receptor 2 (HER2) protein, which makes tumour cells grow. So, if the tumour is HER2 positive, many targeted therapy options exist.

• One of the first drugs, Tamoxifen and Aromatase inhibitors used in treating breast cancer, are directed against ER receptors that form the backbone of Hormonal Therapy. Then came the era of Her2Neu-directed therapy with Trastuzumab and Lapatinib around the millennium, improving patient survival and increasing breast-conserving surgeries. Finally, after a decade, the surge of Immunotherapy and antibody drugs came, again proving a boon for cancer patients. The conjugated monoclonal antibody TDM1 used for Her2Neu-positive patients who progressed on Transtuzumab gave hope in improving survival. The evolution of small molecules like CDK4/6 inhibitors (Palbociclib, Ribociclib, Abemaciclib) in metastatic breast cancer showed improved survival by three years with excellent oral tolerance in older women.
• Similarly, BRCA mutation-positive women now have PARP inhibitors (Olaparib, Rucaparib) to improve cure rates in metastatic and adjuvant settings. In addition, there are several new targeted agents in the pipeline to be available shortly, where we will have more options.

Summary

To summarize, 21st century has changed the landscape of breast cancer treatment, starting from molecular diagnostics, identifying the target or driver mutation, and personalizing therapy with targeted agents to improve cure rates and conserve the breast. So, this October, think pink, think breast cancer awareness.