February 3, 2024 

After the online print of my previous article, many of them had enquired about various types of cancers, mode of spread and information on its management. As a part of cancer awareness initiative and on the occasion of the World Cancer Day, I will be discussing the most common women cancer i.e. breast cancer. 

Breast Cancer or Breast Carcinoma is the most common cancer women suffer in India. Over the decades and population-based cancer data registries, the incidence of the breast cancer has shifted towards the increasing trend. During 1990s, cervical cancer was the leading cancer subsite which was followed by the breast cancer. But since 2000-2003, the scenario has changed with breast cancer overtaking it. As per 2020 Globocan data, in India, incidence of breast cancer cases were 1,78,361 accounting for 13.5% of all the cancer cases and the mortality rate of 90,408 of all the deaths i.e. 10.6%. Based on the prediction model data, it is predicted that breast cancer cases might reach 2,50,000 cases/year by 2030. There is common notion that breast cancer affects only women which is not true and even there are incidence of male breast cancer cases as well. So, how does breast cancer occur? What is the reason or pathophysiology behind it? To answer these questions, one must understand the normal physiology of the breast tissue. 

Physiology and Pathophysiology 

Breast tissue has got two components, ductal and lobular tissues. Lobular tissues are responsible for lactation while the ductal components connect these lobular tissues to form lactiferous ducts to drain the milk during lactation phase or the secretions through the nipple. Breast undergoes cyclical change due of the hormonal variations which occur during the ovarian cycle. The hormonal change which occur in ovarian cycle has impact on uterus as well leading to menstrual cycle. Menstrual cycle involves three phases. Menstrual phase, follicular/proliferative phase and luteal/secretory phase (Figure 1). Menstrual phase in Eumenorrhea individuals with normal and regular menstruation that lasts for around the first 5 days of the cycle, which then proceeds to second phase of the uterine cycle, proliferative phase where the lining of the uterus to grow and proliferate (Figure 1). This occurs due to the estrogen secreted by follicular phase of the ovarian cycle which overlaps with the proliferative phase of the uterine cycle. As the resultant of the latter phases of the proliferative phase, the estrogens initiate the formation of a new layer of endometrium in the uterus. Likewise, these indigenous estrogens cause breast enlargement and ductal growth. On the day 11-14^th due to surge in luteinising hormone, ovulation occurs. The next would secretory phase of menstrual cycle (corresponds to the luteal phase of the ovarian cycle). Here, the corpus luteum in the ovary produces progesterone, which plays a vital role in making the endometrium receptive to the implantation of a blastocyst/fertilized egg. It’s during this phase, ductal maturation and glandular enlargement occurs leading to lumpiness feel in the breast and resultant cyclical breast pain/mastalgia towards the latter part of the secretory/luteal phase or around 10 days prior to the menstruation. If pregnancy does not occur then the ovarian and uterine cycles start all over again. Likewise, the changes in the breast get reversed and new cyclical changes resume (Figure 1). All these cyclical changes are possible due to hormonal receptors (estrogen and progesterone receptors) present in the breast which respond to the hormonal signals from estrogen and progesterone of the ovarian cycle.Sometimes this perfect balance is lost and those changes doesn’t get reversed, this results in lumps and cysts in the breast, which are generally benign and termed as fibrocystic diseases of the breast. In short, any pathologic imbalance between estrogen and progesterone during the menstrual phases causes cellular proliferation. Moreover, oxidative metabolites of estrogen can induce DNA damage and mutations. Repeated impairment of the repair process during cycles, can transform a normal cell into pre-malignant and eventually malignant cell through mutation (Kindly refer my previous article). During the premalignant stage, high proliferation of stromal cells can be activated by estrogen to support the development of breast cancer. 

Breast cancer causes and risk factors 

The primary risk factors for breast cancer are being female and older age.48% of breast cancer are seen in women less than 50 years and the incidence is bit higher in peri-menopausal age group. Other risk factors for developing breast cancer would be hyper-estrogenism disorders like ovarian tumours, genetic conditions like familial hyper-estrogenism disorders, intake of hormonal replacement therapy/HRT medications given for post-menopausal women (risk increases during the intake of medications and subsequently reduces after discontinuation of HRT). High cholesterol, obesity, alcohol intake, smoking, lack of physical activity, exposure to the radiation and genetics like family history of malignancy are all high risk factors for developing breast cancer. Child bearing and lactation are considered as a protective factor since estrogen influence over the breast tissue is reduced during the lactation phase. Earlier consuming oral contraceptive pills were considered to be a risk factor as it had only estrogen content but presently it’s considered safe as it is balanced with progesterone hormonal pills as well. Genetics plays a role in 5–10% of all breast cancer cases. Hereditary breast–ovarian cancer syndrome, Li–Fraumeni syndrome, Cowden syndrome, Peutz–Jeghers syndrome are some of the syndromes which can cause breast cancer along with cancers in other organs in the body. Women with the history of breast and ovary cancer (hereditary breast–ovarian cancer syndrome) in their maternal family has an increased risk of 1.4%. The risk increases if there are more number of affected individuals in the family. Hereditary breast–ovarian cancer syndrome occurs in the individuals who carry the BRCA1 and BRCA2 gene mutation which is basically mutation of tumor suppressor gene (Kindly refer my previous article). One of the popular Hollywood actresses got herself tested positive for this gene, as she had a strong family history of malignancy. Her grandmother and maternal aunt was diagnosed with ovarian cancer and she lost her mother with breast cancer. This prompted her to get tested and underwent prophylactic mastectomy (breast surgery) and salphingo-oophorectomy (removal of ovaries) as a part of risk reducing strategy. 

Symptoms and Investigations 

Breast Cancer usually presents with

• Lump over the breast
• Pain not associated with cyclical mastalgia
• Sometimes it can be painless lump found accidentally while taking bath
• Some patients present with nipple discharge which might be bloody, brownish or green in colour
• While some patients might only have a swelling in the axilla without any of these symptoms.
• If these lumps are not timely intervened or it goes unnoticed; the lumps can increase in size, involve and then erode the overlying skin to form an ulcer. There may be an unusual dimpling of the skin or redness over the breast lump.
• Sometimes the axillary lymph nodes might compress axillary vein or brachial plexus nerves to cause arm edema (swelling) or pain.
• Bony pain, breathelessness/blood in the sputum (phlegm/haemoptysis), abdominal pain/distension are all the symptoms if there are bone, lung and liver/ovarian metastasis. 

Patients having any of these symptoms need to approach a Medical, Radiation or a Surgical Oncologist who would evaluate based on the guidelines. Patient would require to undergo ultrasound/mammogram of both the breasts, guided biopsy of the breast lump for the diagnosis. After confirmatory diagnosis, patient would require to undergo metastatic workup for which either Whole body PET-CT Scan is performed or individually CT Chest, Contrast enhanced CT Abdomen, Bony Scan is done to evaluate if there any distant spread. To assess the hormonal receptor status, Immunohistochemistry tests (for estrogen, progesterone, HER2 receptor status and Ki-67) is performed over the previous biopsy specimen. Based on the results of the IHC, oncologist would be able to plan for the Hormonal and Targeted therapy on the later date. 

Treatment 

Breast cancer treatment involves combination of Surgery, Chemotherapy, Radiation, Hormonal therapy, Targeted and Immunotherapy. The balance and sequence of the therapy is based on the oncologist, who judiciously individualises the treatment protocol based on the reports of the patient. Couple of decades earlier, stage used to play an important role in the prognosis of the disease but currently, along with stage, receptor status also determines the prognosis and cure of the patient! Breast cancer surgeries involves removal of the whole breast and site of its spread i.e. axillary lymph nodes which is called as modified radical mastectomy (Figure 2) or retain the breast, by performing breast conservative surgery. This is possible based on ratio of the tumour volume versus breast volume and accordingly breast conservative surgery with axillary dissection is done. For reconstruction, surgical oncologist would harvest local flaps, regional flap (latissimus dorsi flap) or free flap accordingly to the requirement and to match the volume of the opposite breast. But breast conservative surgery necessitates mandatory radiation to the remainder breast tissue while in the classical case of modified radical mastectomy, radiation is based on the histopathological features of the modified radical mastectomy specimen. Sentinel lymph node biopsy can also been done to avoid formal axillary lymph node dissection and the resultant lymphedema of the arm. 

Chemotherapy acts on all the cells which has a rapid growth cycle, as a result it affects the tumour cells and also, other normal tissue which has relatively rapid turnover like hair, nails, bowel mucosa. That’s is the reason unfortunately, chemotherapy patients have temporary changes in nails, hair loss and diarrhoea. But over the time they recover from these adverse effects. During chemotherapy, eligible patients would receive targeted chemotherapy like Trastuzumab for HER2 receptor positive status and immunotherapy/biological therapy for PDL1 receptor/BRCA positive patients. After completion of the trimodality treatment i.e. surgery, chemotherapy and radiation, response evaluation would be done with PET-CT scan and patient would be given hormonal therapy based on the estrogen and progesterone receptor status for a minimum period of 5 years. I have tried my best, to cover the treatment aspect as short as possible but in reality, the treatment depends on patient, disease and receptor status and accordingly the sequence of treatment varies. Kindly consult an oncologist (Medical, Radiation or a Surgical Oncologist) for an effective treatment plan. In patients with breast cancer, the affected side arm would not be recommended for the intravenous chemotherapy cannulation and such patients can benefit with insertion of peripherally inserted chemotherapy catheter (PICC) or chemoport (Figure 3). The PICC line lies outside the body in the opposite arm for a period of 6 months and requires certain care like restriction of the arm mobility regular dressings and care, while chemoport (as discussed in previous article) lasts for 5 years under subcutaneous with relatively less maintenance and discomfort. This requirement would be guided and inserted by an oncologist (Medical, Radiation or a Surgical Oncologist). 

This article was planned to create awareness of breast cancer and as a continuation of this initiative, I would like stress upon few important points on breast cancer awareness. 

• Stop or reduce alcohol intake. It's safest not to drink alcohol. Its intake directly proportional to risk of developing a breast cancer.
• Maintain a healthy weight. Simple steps may help. Watch your portion sizes. Try to eat fewer calories. Take fruits and vegetables and exercise routinely.
• Get active. Physical activity can help you stay at a healthy weight, which helps prevent breast cancer. Try to get at least 75 minutes of vigorous aerobic/cardio exercise a week like walking, biking, running and swimming.
• Breastfeed. Breastfeeding during physiological lactation phase play an important role in helping women prevent breast cancer. The longer you breastfeed, the greater is the protective effect.
• Avoid Hormone Therapy for Menopause. Both estrogen-only hormone pill and estrogen-plus-progestin hormones increase the risk of breast cancer. If it’s necessary, it should be for the shortest time possible. Always take medications under doctor’s guidance.
• Avoid Smoking. Smoking tobacco raises the risk of breast cancer. Passive smokers also has the risk.
• Breast self-examination.It is a step-by-step method to examine your breast, the look or the feel. By looking at and feeling your breasts regularly, you can notice changes in your breasts better or detect when something feels different. Kindly approach an oncologist, who would perform clinical breast examination and would perform necessary tests based on your medical history. It is better to get self-examination done on monthly basis. Especially women who are menstruating, should perform a breast self-exam after their period ends. Post-menopausal women and those who are having irregular periods, can pick a day each month. Choose a day that’s consistent and easy to remember, like the first day of the month, the last day of the month and record your findings on a booklet or so. The technique to be done is as demonstrated in the figure 4 below. 

Breast cancer screening - A woman is considered to be at average risk if she doesn’t have a personal history of breast cancer or a strong family history of breast cancer.

• Women between 40 and 44 have the option to start screening with a mammogram every year.
• Women 45 to 54 should get mammograms every year.
• Women 55 and older can switch to a mammogram on alternate year 

Women who are at high risk for breast cancer if they have any of the above (although rare) mentioned family history of syndromes or radiation therapy to the chest when they were between the ages of 10 and 30 years and they would require to undergo breast MRI and a mammogram every year, after 30 years of age. 

I hope these basic information is sufficient to guide you on breast cancer, you can approach me if there are any further queries. 

Thank you for patiently going through the article!

Also read:
 

• Decoding Cancer