“I was raising my beautiful children. A year back I landed my dream job. We moved into our newly allotted apartment. Life was pacing at ease. We were content with our lives. After years of education, struggles, and sweats, I was settled. I was healthy, if not fit. One morning, I felt a lump in my right breast. Initially ignored, this lump increased in size with time. I have decided to visit a doctor. I did not know my life was going to be upside down.” Narrates Jasleen Kaur, a young mother of two from a city in India. This is a battle many can relate to.

She rushed immediately to the nearest tertiary care hospital for a checkup. The initial mammograms revealed a dense mass in the right breast suggestive of malignancy. The doctor looked at her and said, “we need to do a confirmatory analysis. When can you provide samples for a biopsy?”

She was already having a tough time digesting the fact that my lump is suspiciously neoplasm. She could do anything doctors would suggest to rule out the possibility of it. She was informed that they will do a core needle biopsy. This scenario got her worried. The surgeon taking the biopsy explained to her the procedure and the aftermath of it. She could understand that the biopsy samples would be taken for pathological assessment. They will examine cell morphology, architecture, and biomarkers for cancer.

The histopathology reporting was done. The desperation on the face of Jasleen was visible. She was accompanied by her husband to the clinic. The oncologist Dr Shukla reviewed the reports and sighed. “Hmm. Mr. Singh, your wife has cancer. TNBC.”

“What? What is TNBC? Will she be, okay?” Mr. Singh asked gasping for breath.

“We will do our best, Mr. Singh. Rest assured. TNBC or Triple Negative Breast Cancer is a type of breast cancer.” Explained Dr Shukla. “Our body needs some chemical substances for growth and sustenance, which we call hormones. Two hormones namely Estrogen and Progesterone play a crucial role in normal female breast development. These hormones enter the cells of the breast and allow them to grow. Our cells have some ‘receptors’ to transmit the signals of these hormones. These hormone receptors (HR): estrogen and progesterone receptors (ER and PR) along with human epidermal growth factor receptor 2 (HER2) serve the purpose of developing the breast cells. Sometimes due to some molecular aberrations, these receptors are present in excess. This contributes towards the unnecessary excessive growth of any part of the breast which ultimately propagates to cancer.“

“Can’t we stop them?” Mr. Singh eagerly asked.

“We can if there is a hormone receptor or ER-positive case of the initial stage.” Dr. Shukla continued. “The presence of HR and HER2 determine the severity and effective treatment plan of cancer. We have some approved drugs against these receptors. For example, if someone is ER/PR/HER2 positive, then we can block these receptors using targeted drugs or prevent the attachment of hormones to these drugs. Unfortunately, your wife has triple-negative breast cancer, where these receptors are negligible or absent. So, targeted therapy is out of the question here.”

“What happens now?” Mr. Singh’s desperation increased.

“Don’t worry Mr. Singh. Even if we do not have specific therapy, we will try to shorten the tumor with chemotherapy. This is an effective way to kill the malignant cells. Targeting the actively dividing cells through chemotherapy may lead to significant hair fall, weight loss, and fatigue, among others. However, looking at the severity of Ms. Kaur’s case, we need to operate on her with MRM; modified radical mastectomy, a form of breast removal surgery. This will significantly reduce the risk of cancer in your body.” Dr. Shukla explained the further procedure.

“But couldn’t we detect the severity of breast cancer earlier?” asked a curious Mr. Singh.

“That is a valid research question, Mr. Singh.” Said Dr. Shukla. “For this, we need to identify crucial prognostic biomarkers that would detect and predict the aggressiveness of cancer. One such research is based on Androgen Receptor (AR); another hormone receptor present in the breast cells. Studies have shown the presence of AR in about 70-90 percent of breast cancer. Research is currently underway to explore therapeutic and prognostic relevance. You can be part of this research if you wish.”

“Hmm” sighed Mr. Singh.

As per World Health Organization official data, India has more than 13.24 lakh new cancer cases in 2018. The biggest contributor to this data is breast cancer, the most prevalent form of cancer in India topping the incident and mortality figures. The majority of India resides in villages, which hinges on the foundation of social ethics and culture. These cultural aspects of society stigmatize the expression of such maladies. This explains the delayed presentation of breast cancer cases in women in India.

The chemotherapy began. So began the struggles of Ms. Kaur. The frustration and uncertainty dominated her physical and mental health. If breast cancer does not kill you, it murders your morale, crushes your confidence, and affects your lifestyle.

“Ms. Kaur. Cancer is a battle fought on two fronts. Inside and outside. Please take precautions, and I will do my best at the molecular level. Together we shall overcome.” Dr Shukla assures her in his calming voice.

During surgery, a part of the tumor was taken after the informed consent. This was subjected to researching the expression profile of androgen receptors. AR is a hormone receptor that is abundantly expressed in breast cancer. It binds to intracellular androgens and catalyzes the expression of androgen-responsive genes. Molecular analysis reveals there are variants of the AR protein. One such AR-variant, AR-V7 protein has been shown to confer aggressive behavior in prostate cancer. Cellular studies have revealed a prominent expression of AR-V7 in breast cancer. There is a positive correlation observed between aggressive behavior and expression of AR-V7 in clinical breast cancer samples. Currently, research is underway to validate the role of AR-V7 in clinical utility and biomarker of an aggressive phenotype in breast cancer.

After consulting the doctors, Jasleen Kaur underwent radiation therapy post-surgery which destroys the remaining cancer cells. She adheres to the prescribed medications and regular physical exercises as recommended. Her race to recovery begins. This requires a lifelong commitment to a modified lifestyle, exercise, and frequent mammograms. Her close kins are now aware of genetic predisposition in cancer. They now understand the importance of immediate medical attention for any external and internal changes in the body. The amendment in their lifestyle and regular screening of breast from itself or by the trained clinician may detect the early onset of cancer.

Annually lakhs of females are diagnosed with breast cancer in India. A majority of these patients present at a later stage. Due to the lack of prognostic biomarkers of aggressive behavior, a significant fraction of these patients succumb to breast cancer in India. This contributes to more incidence to mortality ratio of breast cancer in India. The research work narrated in the story aims to establish the prognostic value of AR and its splice variants. These biomarkers can be incorporated for routine examination and assist clinicians in the better management of breast cancer in India.

Om Sarve Bhavantu Sukhinah, Sarve Santu Niramayah!!