An overview of changing paradigm of Breast Cancer

Oct 27,2023

Breast cancer is the commonest cancer in women globally. In recent past, with an exponential rise in cases, it has outdone lung cancer as the most common cancer worldwide. As per the last GLOBOCAN (Global Cancer Burden and Strategies for Cancer Control) data released in 2020, it constituted 24.5 % of new cancer cases in women and 11.7% of new cancer cases in both sexes. It has shown an increased prevalence even in Asian countries including the Indian subcontinent. In India, breast cancer has long replaced cervical cancer as the leading cause of cancer and cancer related deaths in women forming nearly one third of all cancer cases detected in Indian women. With such a heavy case burden, it is imperative to know the disease in detail to be able to not only understand the factors that are responsible for its causation so that it can be prevented but also to be able to treat it effectively with the best therapeutic options having a curative goal in mind.

Unlike earlier times, when breast cancer was thought to be a single disease, recent advances in molecular basis of cancer have revealed breast cancer to be classified based on individual genetic signature for each patient. Thus, even the analysis of risk of recurrence and management is no longer a ‘one size fits all’ approach. It needs a careful evaluation of the disease in a personalised manner for each patient, understanding the molecular biology and mutations which can be targeted with precision for that particular individual.

The etiopathogenesis of breast cancer is multifactorial. Gene mutations play a major role in hereditary breast cancer. Women with BRCA1 or BRCA2 gene mutations have nearly a 7 in 10 chance of getting breast cancer by age 80. This risk also increases with more first-degree relatives having the disease. Such patients are susceptible to disease causation at a younger age and involving both breasts. They further have an increased likelihood of developing other cancers like ovarian and pancreatic to name a few which are also associated with mutations in the genes. Other genes like PALB2, TP53, ATM, PTEN and CHEK2 which are implicated in causation of breast cancer are less frequently mutated.

Non genetic factors also play an important role in the pathogenesis of breast cancer. Increasing age, early menarche, late pregnancy, late menopause, high calorie diet, smoking and exposure to exogenous hormones like in post-menopausal hormone replacement therapy, are all such factors associated with an increased risk of developing breast cancer. In developed areas and urban population, IVF and implant associated breast cancer is coming up as an important area of concern, although the incidence particularly with newer implants is negligible.

One of the factors which plays a cardinal role once a patient is diagnosed with breast cancer is the hormone receptor and target gene status of the tumor. Commonly breast cancers are divided into various subtypes based on expression of Estrogen Receptor (ER), Progesterone Receptor(PR), HER2 protein and their intrinsic proliferative activity determined by the Ki67 index. Cancers which show ER and PR positivity with low Ki67 index are less aggressive and easy to treat with hormonal treatment. Cancers showing increased levels of HER2 expression are more aggressive but respond well to anti-HER2 targeted treatment with a drug called Trastuzumab. But cancers which are negative for ER, PR and HER2 expression are called triple negative breast cancers and are the most aggressive and onerous to treat. The disease course is marked by cancer spreading to other parts of the body (metastasis) early in the course and treatment outcomes being dismal.

The diagnosis of breast cancer has come a long way from diagnosing the histological subtype to profiling the genomic signature of each case and analysing recurrence risk by various international and nationally standardized tests. Genome sequencing is slowly progressing to becoming a norm rather than exception. Artificial intelligence is also playing an increasing role in numerous areas particularly objective assessment of hormone/protein expression, Ki67 index and genomics in breast cancer.

There have also been many advances in treatment with the advent of newer modalities and a multidisciplinary approach. Chemotherapyfor metastatic breast cancer has evolved from drugs like cyclophosphamide and methotrexate to taxanes. The radiation treatment indicated in loco-regional breast cancer has progressed from 2D to 3D and accelerated partial breast irradiation, reducing the treatment exposure time and toxicity. Surgery has also advanced from the days of whole breast removal to a highly conservative and cosmetic approach. Advent of targeted therapy and immunotherapy has drastically improved the paradigm of cancer care and breast cancer is no exception with promisingly improved treatment benefit and survival.

In India, as per a recent study, 30% of the cases occur in women younger than 40 years of age. The disease is also more aggressive with a higher percentage of cases being tripe negative. Nearly 2/3rd of cases present in late stages because of lack of awareness and screening programmes. This deficit is particularly seen as lack of self-breast examination, less awareness about screening facilities like mammography being available even in government hospitals and usually late presentations only when a big mass is palpable due to negligence and the mass itself usually being painless. Other factors which conspicuously stand out as a part of the problem are deficient awareness even in healthcare providers, delay in diagnosis and treatment, social implications with stigma and guilt of some wrongdoing being associated with cancer particularly in rural areas, cost implications, distance from an adequate healthcare facility and lack of manpower and resources with only few hundred oncologists being available per million population in the country and only few centres in public sector providing holistic, adequately integrated cancer management while private care is available primarily in bigger cities and is extremely expensive. In light of all these factors, breast cancer has now become an exponentially increasing public health crisis.

Source: Health World