Breast Cancer Treatment: Recent Trends and Advancements

DR MANZOOR AHMAD MIR

Breast cancer (BC) is A cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). Breast cancer is the most common type of cancer in women worldwide. With an anticipated 2.3 million new cases, or 11.7% of all cancer cases, it has now surpassed lung cancer as the most common type of cancer worldwide in 2021. According to epidemiological studies, by the year 2030, there would be over 2 million cases of BC worldwide. According to Globocan, data for 2020, breast cancer caused 10.6% of all fatalities and 13.5% of all cancer cases in India. In India, patients with breast cancer have a worse chance of survival compared to Western nations because of early age at onset, advanced illness at presentation, a delay in the start of decisive management, and insufficient or fragmented care.

   

Breast cancer is not just a disease that affects married people; according to the Regional Cancer Center, young women who are not yet married are developing the disease at a higher rate. Of course, women are more likely than men to develop breast cancer. Most cases of breast cancer have been reported during the year 2020-21, followed by lung cancer”. An estimated 30% of breast cancer cases are attributed to modifiable risk factors, such as physical inactivity, excess body weight, alcohol intake, poor diet and thus may be preventable. Secondary prevention through mammography screening can further prevent death, and alongside advances in treatment, is attributed with substantial reductions in breast cancer mortality. A recent 2018 survey found that rate of breast cancer among women in Kashmir valley was 13.5%. In an alarming development Kashmir has witnessed a 20% rise in cancer cases in a single year, with breast cancer accounting for the majority of cases and affecting more unmarried women as reported by Kashmir’s top tertiary care facility, Sheri-e-Kashmir Institute of Medical Sciences (SKIMS), Soura Srinagar. This is really alarming that breast cancer is the leading cancer among women in Kashmir and that younger females are affected more than older ones. Experts contend that the primary cause of the rising number of breast cancer sufferers is attributed to people’s changing lifestyles, physical inactivity, obesity, lack of breast feeding, late marriages and on top of that lack of awareness among masses and absence of a robust breast cancer screening program.

Breast Cancer Screening

Screening means looking for the disease before a person has developed any signs and symptoms. This can in turn help find breast cancer at an early stage. If any change or abnormality is detected early in breast, it may be easier to manage and treat the disease with greater chances of success. By the time breast cancer signs and symptoms start appearing, it may have begun to spread and may become more difficult to treat with increasing health care costs and shortening lifespan. Breast screening is a method of detecting breast cancer at a very early stage. A mammogram is the first step in screening. It is a low dose x-ray in which each breast is placed in turn on the x-ray machine and gently but firmly compressed with a clear plate. This lasts for a few seconds and is harmless. The mammograms are examined thoroughly and the results sent to the woman and her practitioner. The mammogram can detect small changes in breast tissue that may need further investigations to check for breast cancer.  Usually, the women aged 50 plus should go for routine mammogram screening as after menopause the glandular part of the breast reduces and is replaced by fatty tissues. This makes the breast less dense and makes interpretation with mammograms easier. However, it is better for younger women and women with denser breasts to go for digital mammography as it is equally effective as film mammography in older women. If the mammograms show positive findings, the patient is asked to return for further investigations which may include a clinical examination using breast ultrasound which uses sound waves to produce images to determine whether a new breast lump is a solid mass or a fluid-filled cyst, an MRI which unlike other types of imaging tests, doesn’t use radiation to create the images,  and instead uses magnet and radio waves to create images of the interior of the breast, core biopsy or fine needle aspiration or open or excisional biopsy where a specialized needle device guided by X-ray or another imaging test is used to extract a core of tissue from the suspicious area. Samples of biopsy are sent to a laboratory for investigation and analysis where experts determine whether the cells are cancerous. Once breast cancer is diagnosed the next step is to find of what grade and stage your breast cancer is and further whether the cancer cells have hormone receptors or other receptors that may influence the treatment options.  Breast cancer stages range from 0 to IV with 0 indicating cancer that is noninvasive or contained within the milk ducts. Stage IV breast cancer, also called metastatic breast cancer, indicates cancer that has spread to other areas of the body. To establish the stage of breast cancer the things which need to be taken into account are the cancer’s grade; the presence of tumor markers, such as receptors for estrogen, progesterone and HER2; and proliferation factors. To know the stage of breast cancer various tests and procedures are employed and mainly include blood tests, like complete blood count, mammogram of the other breast to look for signs of cancer, MRI of Breast, positron emission tomography (PET) scan and computerized tomography (CT) scan. But it is pertinent to mention here that a woman need not to undergo all of these tests and it is your health practioner or doctor who selects the appropriate screening methods and tests based on your specific circumstances and taking into account your symptoms and signs.

Management of breast cancer:

Since last two decades, breast researches have led to extraordinary progress and pathbreaking findings in our understanding of the breast cancer disease, resulting in more efficient and less toxic treatments. In addition to this the enhanced public awareness and upgraded screening have led to earlier diagnosis at stages acquiescent to complete surgical resection and curative therapies. The leading prognosticators of breast cancer are the individual attributes and genetic traits of older age, family history of two or more first-degree relatives with breast cancer, and breast density; inherited genetic mutations such as BRCA1 and BRCA2, a secondary array of risks mainly pertain to hormonal therapy among older women; obesity, and consequent early menarche resulting from lifestyle behaviors such as poor diet and lack of exercise among young girls and the environmental factors like exposure to contaminants at home, work, and local areas.

Breast Cancer management is multidisciplinary and has advanced significantly. Breast cancer treatment options are based on type of breast cancer, grade and stage of breast cancer, size, and whether your breast cancer cells are sensitive to hormones or not. Before starting a management cum treatment plan a patient’s overall health, status of immune system and the patient’s own preferences are also taken into account. Most women undergo surgery for breast cancer and many also receive additional treatment after surgery, such as chemotherapy (Neo-adjuvant, adjuvant or palliative), hormone therapy or radiation. Chemotherapy might also be used before surgery in certain situations. Mastectomy followed by adjuvant chemotherapy was once a common course of treatment for locally advanced BC, triple-negative breast cancer, and tumors expressing HER2. Currently, it combines both a systemic therapy method that targets the entire body and a loco-regional approach that uses surgery and radiation therapy to focus on just the tumor. Endocrine therapy, chemotherapy, anti-HER2 therapy, polymerase inhibitors for BRCA (breast cancer gene) mutation carriers, and, more recently, immunotherapy are all examples of systemic therapy.

Breast cancer treatment

According to the World Cancer Report 2020, early detection and prompt treatment are the most effective interventions for BC management. Early detection of breast cancer is the key to success. As per the latest studies the success of breast cancer treatment and survival depends on the early detection. According to a study, the 5-year overall survival rate was 95% for patients in stage I, 92% for patients in stage II, 70% for patients in stage III, and just 21% for patients in stage IV. The biology and behavior of breast cancer also affects the treatment plan. Some tumors are smaller but grow quickly, while others are larger and grow slowly. Treatment options and recommendations are very personalized and depend on several factors, including: The tumor’s subtype, including hormone receptor status (ER, PR), HER2 status, and nodal status, the stage of the tumor, Genomic status, the patient’s age, general health, menopausal status, and patients own preferences. Since last two decades, breast cancer researches has led to extraordinary progress in our understanding of the disease, resulting in more efficient and less toxic treatments.

The common types of treatments used for early-stage and locally advanced breast cancer are:

Surgery

Surgery is the removal of the tumor and some surrounding healthy tissue during an operation. Surgery is also used to examine the nearby axillary lymph nodes, which are under the arm. Generally, the smaller the tumor, the more surgical options a patient has. The types of surgery for breast cancer include the following:

Lumpectomy: This is the removal of the tumor and a small, cancer-free margin of healthy tissue around the tumor. Most of the breast remains. For invasive cancer, radiation therapy to the remaining breast tissue is often recommended after surgery, especially for younger patients, patients with hormone receptor-negative tumors, and patients with larger tumors. A lumpectomy may also be called breast-conserving surgery, a partial mastectomy, a quadrantectomy, or a segmental mastectomy.

Mastectomy: This is the surgical removal of the entire breast. A mastectomy is a way to treat breast cancer by surgically removing a breast and sometimes nearby tissues. For a while, the standard treatment for breast cancer was a radical mastectomy, with total removal of the breast, lymph nodes in the underarm, and some chest muscles under the breast. But surgical advances have given people more options than ever.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells.

There are several different types of radiation therapy:

External-beam radiation therapy: This is the most common type of radiation treatment and is given from a machine outside the body. This includes whole breast radiation therapy and partial breast radiation therapy, as well as accelerated breast radiation therapy, which can be several days instead of several weeks.

Brachytherapy: This type of radiation therapy is given by placing radioactive sources into the tumor. Although the research results are encouraging, intra-operative radiation therapy and brachytherapy are not widely used. Where available, they may be options for a patient with a small tumor that has not spread to the lymph nodes.

Partial breast irradiation: Partial breast irradiation (PBI) is radiation therapy that is given directly to the tumor area instead of the entire breast. It is more common after a lumpectomy. Targeting radiation directly to the tumor area usually shortens the amount of time that patients need to receive radiation therapy. However, only some patients may be able to have PBI.

Intensity-modulated radiation therapy: Intensity-modulated radiation therapy (IMRT) is a more advanced way to give external-beam radiation therapy to the breast. The intensity of the radiation directed at the breast is varied to better target the tumor, spreading the radiation more evenly throughout the breast. The use of IMRT lessens the radiation dose and may decrease possible damage to nearby organs, such as the heart and lung, as well as lessen the risks of some immediate side effects, such as peeling of the skin during treatment.

Proton therapy: Standard radiation therapy for breast cancer uses x-rays, also called photon therapy, to kill cancer cells. Proton therapy is a type of external-beam radiation therapy that uses protons rather than x-rays. At high energy, protons can destroy cancer cells. Protons have different physical properties that may allow the radiation therapy to be more targeted than photon therapy and potentially reduce the radiation dose. The therapy may also reduce the amount of radiation that goes near the heart.

Therapies using medication

Effective therapy of breast cancer requires maximum therapeutic efficacy, with minimal undesirable effects to ensure a good quality of life for patients. The cautiously selected combination of therapeutic agents provides patients with the prospect to derive maximum benefit from therapy while minimizing or eliminating resistance, recurrence and toxic effects, as well as ensuring that patients have a good quality of life and longer survival. The treatment plan may include medications to destroy cancer cells. Medication may be given through the bloodstream to reach cancer cells throughout the body. When a drug is given this way, it is called systemic therapy. Medication may also be given locally, which is when the medication is applied directly to the cancer or kept in a single part of the body. The types of medications used for breast cancer include: Chemotherapy, Hormonal therapy, Targeted therapy, Immunotherapy.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells. It may be given before surgery to shrink a large tumor, make surgery easier, and/or reduce the risk of recurrence. When it is given before surgery, it is called neoadjuvant chemotherapy. It may also be given after surgery to reduce the risk of recurrence, called adjuvant chemotherapy. There are many types of chemotherapy used to treat breast cancer. Common drugs include: Docetaxel (Taxotere), Paclitaxel (Taxol), Doxorubicin (available as a generic drug), Epirubicin (Ellence), Capecitabine (Xeloda), Carboplatin (available as a generic drug), Cyclophosphamide (available as a generic drug), Fluorouracil (5-FU), Methotrexate (Rheumatrex, Trexall), A patient may receive one drug or a combination of different drugs given at the same time to treat their cancer. Research has shown that combinations of certain drugs are sometimes more effective than single drugs for adjuvant treatment. For early-stage and locally advanced breast cancer, the following drug combinations are used: AC (doxorubicin and cyclophosphamide), EC (epirubicin, cyclophosphamide), AC or EC followed by T (paclitaxel or docetaxel), or the reverse, CAF (cyclophosphamide, doxorubicin, and 5-FU), CEF (cyclophosphamide, epirubicin, and 5-FU), CMF (cyclophosphamide, methotrexate, and 5-FU), The side effects of chemotherapy depend on the individual, the drug(s) used, whether the chemotherapy has been combined with other drugs, and the schedule and dose used. These side effects can include fatigue, risk of infection, nausea and vomiting, hair loss, loss of appetite, diarrhea, constipation, numbness and tingling, pain, early menopause, weight gain, and chemo-brain or cognitive dysfunction.

Hormonal therapy

Hormonal therapy, also called endocrine therapy, is an effective treatment for most tumors that test positive for either estrogen or progesterone receptors (called ER positive or PR positive. This type of tumor uses hormones to fuel its growth. Blocking the hormones can help prevent a cancer recurrence and death from breast cancer when hormonal therapy is used either by itself or after chemotherapy. 

Hormonal therapy for breast cancer treatment is different than menopausal hormone therapy (MHT). MHT may also be called postmenopausal hormone therapy or hormone replacement therapy (HRT). Hormonal therapies used in breast cancer treatment act as “anti-hormone” or “anti-estrogen” therapies. They block hormone actions or lower hormone levels in the body.

Types of hormonal therapy used against breast cancer:

Tamoxifen: Tamoxifen is a drug that blocks estrogen from binding to breast cancer cells. It is effective for lowering the risk of recurrence in the breast that had cancer, the risk of developing cancer in the other breast, and the risk of distant recurrence. Tamoxifen works in people who have been through menopause as well as those who have not

Aromatase inhibitors (AIs). AIs decrease the amount of estrogen made in tissues other than the ovaries in post-menopausal people by blocking the aromatase enzyme. This enzyme changes weak male hormones called androgens into estrogen when the ovaries have stopped making estrogen during menopause. These drugs include Anastrozole (Arimidex), Exemestane (Aromasin), and Letrozole (Femara).

Targeted therapy

Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. These treatments are very focused and work differently than chemotherapy. This type of treatment blocks the growth and spread of cancer cells and limits damage to healthy cells. The first approved targeted therapies for breast cancer were hormonal therapies. Then, HER2-targeted therapies were approved to treat HER2-positive breast cancer.

Immunotherapy

Traditional treatments for breast cancer include chemotherapy, radiation, and surgery. Hormonal therapy, which can reduce levels of estrogen and progesterone, may also be used to prevent disease recurrence in women with hormone receptor-positive tumors. Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are several immunotherapy options for patients depending on their tumor type. Immunotherapy is a relatively new breast cancer treatment that uses your immune system to identify, target and cripple breast cancer cells. While chemotherapy and radiation therapy are still standard breast cancer treatments, healthcare providers are optimistic about immunotherapy’s potential to treat recurring breast cancer, metastatic breast cancer and triple-negative breast cancer.

Palliative or Supportive care

Chemotherapy has many toxicities associated with it and to combat toxicities of breast cancer treatment supportive care arose and it has now got established as a medical specialty dedicated to helping patients with breast cancer. Palliative care is specialized medical care that focuses on providing relief from pain and other symptoms of a serious illness of breast cancer. Palliative care specialists like team of doctors, nurses and other specially trained professionals work with a breast cancer patient, her family and her other doctors to provide an extra layer of support that complements her ongoing treatment and care. Palliative care is used while undergoing other aggressive treatments, such as surgery, chemotherapy or radiation therapy. When palliative care is used along with all of the other appropriate treatments, people with breast cancer may feel better and live longer.

Breast Cancer Awareness: The Key Factor

Awareness is the key to success. Breast cancer awareness is an effort to raise awareness and reduce the stigma of breast cancer through education on symptoms and treatment. The goal of this campaign is to raise the public’s “brand awareness” for breast cancer, its detection, its treatment, and the need for a reliable, permanent cure. It is associated with individual generosity, faith in scientific progress, and a positive and optimistic “can-do” attitude. As general public relies on media as a leading resource for health information and that media messages contribute to health knowledge. As the information disseminated via newspapers and news articles in the print media potentially are influential due to the factors of retrievability, depth, agenda setting and credibility. So, focusing on sources of breast cancer impact, surveys of female college students and their mothers indicate that exposure to breast cancer stories in newspapers and newsmagazines is related to breast self-exam and clinical screening showed that the quantity of mammogram screening coverage in newspapers contributes to mammography utilization. Therefore, the need of the hour is to spread the breast cancer awareness among common masses through whatever channels possible so that breast cancer can be detected at early stages and lives saved.

In this context Department of Bioresources, University of Kashmir is observing Breast Cancer Awareness month at the University of Kashmir and is organizing different Breast Cancer Awareness events and seminars in different colleges of the valley besides raising awareness through print and electronic and social media. The Department is organizing a megaevent of Free Breast Cancer awareness and Screening camp on 31st of October 2022 where the Breast Cancer Awareness Website will be launched besides documentary regarding Breast cancer awareness with special reference to Kashmir valley will be screened for General public.

Dr Manzoor Ahmad Mir (Ph. D, FRSB), Head Department of Bioresources, University of Kashmir

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