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Breast Cancer

Breast cancer is the most common type of cancer in women in both developed and developing countries.

Breast cancer is the most common type of cancer in women in both developed and developing countries. According to the WHO, the global cancer burden is estimated to have risen to 18.1 million new cases and over 9.6 million deaths in 2018. It is estimated that worldwide over 5 lakh women died in 2011 due to breast cancer.

Globally, about 10% of the breast cancer cases are genetic or due to an inherited DNA mutation. The increasing cancer burden may be due to several factors, including population growth and ageing as well as the changing prevalence of certain causes of cancer that are linked to social and economic development.

Breast cancer typically shows no symptoms when the tumor is small, therefore screening is important for early detection. Self-diagnosing is an important part of breast cancer screening strategy.

Breast cancer signs and symptoms include:
• Changes in the size and shape of the breasts
• A lump or swelling in the breasts, upper chest or armpit that feels thicker than the rest of the breasts
• A change in skin texture
• An unusual discharge
• Pain in the breasts that persists over a long period of time
• Redness, soreness, or rash

Tests for diagnosing breast cancer include, diagnostic mammography, breast ultrasound, magnetic resonance imaging (MRI) and biopsy.

The treatment plan is based on the stage and characteristics of cancer depending upon its stage, menopause status, hormone status of cancer, age, overall health.

Surgery:
Breast surgery could be of different types and depends on the size and location of the tumour and its spread to the lymph nodes. Surgery for breast cancer includes breast-conserving surgery (lumpectomy or partial mastectomy) and full mastectomy.

Chemotherapy:
Not all women with breast cancer will need chemotherapy, but in several situations, chemo may be recommended:
After surgery (adjuvant chemotherapy)
Adjuvant chemo is used to try to kill cancer cells that might have been left behind or have spread but can’t be seen, even on imaging tests. If these cells were allowed to grow, they can form new tumours in other parts of the body. Adjuvant chemo can lower the risk of recurrence.

Before surgery (neoadjuvant chemotherapy)
Neoadjuvant chemo may be used to shrink the tumour size so it can be removed with less extensive surgery. It is often used to treat tumour that is too big to be removed by surgery at the time of diagnosis.

For advanced breast cancer
It can be used as the main treatment if the cancer has spread outside the breast and lymph nodes.

As per American cancer society, drugs used for adjuvant and neoadjuvant chemotherapy are:

Doxorubicin acts by stopping or slowing the growth of cancer cells by blocking the enzyme (protein) topoisomerase 2 which is essential for growth of cancer cells. It is given as an IV drip (into your blood through blood vessels)

As a part of anthracyclines group, epirubicin also acts by stopping or slowing the growth of cancer cells through topoisomerase 2. This drug is also given intravenously.

Cancer cells divide themselves and grow, microtubules are essential for forming body of the cells after division. Taxens acts by disrupting microtubules and thus inhibiting the division of cancer cells.

Synthesis of DNA is another important factor of cancer cell division and growth.  5-fluorourac primarily inhibits the enzyme thymidylate synthase blocking the thymidine formation required for DNA synthesis, thus inhibiting the cells growth.

The metabolite of cyclophosphamide called ‘phosphoramide mustard’ that forms DNA cross links within cancer cells that leads to cell death, apoptosis.

Carboplatin has the ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing cell death in cancer cells.

Chemotherapeutic agents used in advanced breast cancer are:

• Taxanes, such as paclitaxel, docetaxel, and albumin-bound paclitaxel
• Anthracyclines (Doxorubicin, pegylated liposomal doxorubicin, and Epirubicin)
• Platinum agents (cisplatin, carboplatin)
• Vinorelbine: Acts by inhibition of cell division through interaction with tubulin.
• Capecitabine: Capecitabine gets metabolised to 5-FU which is a thymidylate synthase inhibitor, required for the de novo synthesis of DNA. Thus, inhibiting the cell growth.
• Gemcitabine: It acts by inhibiting nucleic acid synthesis essential for cell division.
• Ixabepilone: Ixabepilone binds to ß-tubulin subunits on microtubules, leading to suppression of the dynamic instability of aß-II and aß-II microtubules leading to tumour cell death.
• Eribulin: It is also a microtubule inhibitor; it works by stopping the division (mitosis) cancer cells

Radiation therapy:

The need for radiation therapy depends on the type of surgery required, whether the cancer has spread to the lymph nodes or elsewhere in the body, and age. Radiation therapy is mostly given after breast-conserving surgery or in some cases, after a mastectomy.

Hormone therapy:

Some types of breast cancer may be affected by hormones in the blood. ER-positive and PR-positive breast cancer cells grow with exposure to estrogen, which helps them grow. Hormone therapy, for e.g tamoxifen, is a form of systemic therapy, that reaches cancer cells almost anywhere in the body and not just the breast. It can also be used to treat metastatic cancer and cancer relapse.

Targeted therapy:

Trastuzumab, a monoclonal antibody, is used to treat breast cancer that is HER2 receptor positive. It may be used by itself or together with other chemotherapy medication

Useful links:
• https://www.who.int/cancer/detection/breastcancer/en/index1.html
• https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2017-2018.pdf
• https://www.mayoclinic.org/diseases-conditions/breast-cancer/diagnosis-treatment/drc-20352475
• https://www.nationalbreastcancer.org/breast-cancer-treatment
• https://www.who.int/cancer/detection/breastcancer/en/index3.html
• https://www.cdc.gov/cancer/breast/basic_info/diagnosis.htm
• https://www.cancer.net/cancer-types/breast-cancer/diagnosis
• https://www.cancer.ca/en/cancer-information/cancer-type/breast/prognosis-and-survival/?region=on

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