Breast Cancer Awareness

Breast cancer is one of the most common cancers worldwide’. Approximately 200,000 women were affected in the year 2022 in India itself. Today we have the tools to fight breast cancer effectively especially if detected early. While prolonging life has always been the standard against which treatment was measured increasing importance is being paid to quality of life and the patients emotional journey post a diagnosis.

A lot of development has been seen in breast cancer. Favorable outcomes are greater due to the vast options available to a patient, post diagnosis. A close watch for signs and symptoms is emphasized as it may begin with an innocuous breast lump. Ductal carcinoma in situ (DCIS) is recognized as a precursor to invasive breast cancer, while lobular carcinoma in situ (LCIS) is considered a risk factor for its subsequent development. Once invasive, the cancer can be staged as being early, advanced, or metastatic. Early breast cancer has a relatively good prognosis but in the advanced stage the survival rate is poorer and dops significantly upon metastasis due to the wide dissemination of cancer cells.

Traditionally chemotherapy was used as there were fewer treatment options and targets available for therapy. It is still being used quite rampantly, especially in the low socio- economic setting but is no more the focus of active development. While highly effective in killing cancer cells due to its toxicity it kills normal cells as well. Today, targeted therapy is being advocated for as both extracellular and intracellular targets have been identified with a plethora of treatments available. It also helps healthcare professional delay, and sometimes altogether avoid, having to expose their patients to the side effects of chemotherapy.

Targeted therapy, just as the name suggests can focus its action on tumor cells. Hormone therapy targets the hormone receptors while antibodies such as Trastuzumab target HER 2 receptors and bring about their action through downstream signaling. These receptors are structures on the surface of a cell which are expressed in limited quantities on normal cells and overexpressed in cancer cells. Selective Estrogen Receptor Modulators (SERM’s) such as Tamoxifen, Selective Estrogen Receptor Degraders (SERD’s) such as Fulvestrant, Aromatase Inhibitors (Al) such as Anastrozole and Letrozole constitute most of the hormone therapy used in combination with Cyclin Dependent Kinase 4/6 inhibitors such as Palbociclib, Ribociclib and Abemaciclib as frontline therapy in hormone positive (HR+) patients.

Immunohistochemistry (IHC) is a test routinely employed upon diagnosis. The patient is scored on a from 0 to 3+. A score of 3+ and 2+ with in situ hybridization (ISH) + would mean overexpression of HER 2 and classify the patient as HER 2 Positive. This confers a certain amount of aggressiveness to the tumor and a predilection for developing brain metastasis. It also means that the patient would derive the largest quantum of benefit from anti-HER 2 therapies. A score of 2+ ISH- and 1+ would classify the patient as HER 2 Low and would still derive significant benefit from antibody drug conjugate (ADC) therapy. Some newer ADC’s being employed are Trastuzumab Deruxtecan (T-DXd) and Sacituzumab Govitecan (SG) with various treatments being investigated within this category.

There are also patients who do not benefit from these commonly tested targets as they do not possess the receptors for them. They are termed Triple Negative Breast Cancer (TNBC) patients. It has the poorest prognosis and few treatment options due to its heterogeneity and unpredictable behavior. Global statistics suggest TNBC accounts for 10% of breast cancer cases. In India more than 30% of women with breast cancer suffer from TNBC.3 It generally affects younger and pre-menopausal woman unlike the typical post-menopausal elderly woman who is HR+.

Research and deeper understanding behind aspects of cancer have found intracellular targets such as PI3K/AKT/PTEN pathway targeted by drugs such as Capivasertib or Alpelisib while mTOR is targeted by Everolimus. BRCA mutants (particularly high in TNBC) benefit from Poly (ADP) Ribose Polymerase (PARP) inhibitors such as Olaparib. Using these drugs in combination is also a strategy being explored and adopted as is the case of PARP inhibitors with Platinum chemotherapy. A relatively newer approach more frequently adopted in TNBC is the use of immunotherapy which boosts the immune system to targets and kill cancer cells. Drug such as Pembrolizumab are now available and should the patient qualify for its use show significant results in the TNBC space.

In time the growing arsenal of targets and therapies will revolutionize the way we perceive breast cancer, upend several guidelines, and modify physicians’ approach to therapy, all in favor of patients however till then and even beyond prevention remains a robust strategy in our fight against breast cancer. Early detection with simple techniques such as self-breast examination and education on the importance of and access to screening will ultimately bring us a step closer to eradicating the disease altogether.

References:

1. Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2024). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int (accessed October 2024).
2. Timbres J, Kohut K, Caneppele M, Troy M, Schmidt MK, Roylance R, Sawyer E. DCIS and LCIS: Are the Risk Factors for Developing In Situ Breast Cancer Different? Cancers (Basel). 2023 Sep 2;15(17):4397. doi: 10.3390/cancers 15174397. PMID: 37686673; PMCID: PMC10486708.
3. Rekha Vijay Kumar, et al. Estrogen receptor, Progesterone receptor, and human epidermal growth factor receptor-2 status in breast cancer: A retrospective study of 5436 women from a regional cancer center in South India. South Asian J Cancer. 2018 Jan-Mar; 7(1): 7-10