Written by

Marwan ElBagoury	Ahmed Elagouz
Alexandria University, Pharmacy graduate (2006), Bachelor of Law graduate (2018), M.Sc. of Advanced Oncology (2018). He has many scientific papers published and over ten years of experience in multinational biotechnology companies. Dr ElBagouray is a member of the International Society for Pharmacoeconomics and Outcomes Research.	Graduated from the faculty of Pharmacy, October 6 University, Egypt 2005. He has more than 10 years of experience in different roles in multinational pharmaceutical and biotechnology companies within the Middle East region. Currently, he is pursuing his MBA program in the University of the people, United States.

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Breast cancer: Introduction

Breast cancer is one of the most frequent cancers worldwide, and the most common malignancy among women (21% of all new cancer cases). Incidence rates are high in all developed countries, except Japan, and highest in North America.¹

Age is the utmost significant risk factor for breast cancer. A white woman aged 60-years-old is 14 times as likely to develop breast cancer in a single year than a 30-year-old white woman. Two thirds of all breast cancer cases occur after menopause.²

The cumulative lifetime risk of developing breast cancer is about 12% for a woman in North America, but the risk of death from the disease is only 3.6%. The cumulative probability of developing breast cancer increases with age.³

Breast cancer diagnosis by race

Figure 1: The percent distribution of breast cancer cases in women by race at diagnosis. Adapted from gis.cdc.gov ^4,5

Breast cancer incidence rates in the Middle East

Although breast cancer is the most common type of female cancer throughout the Middle East, many women do not seek medical care promptly. Consequently, the region has increased rates of late incidences.⁶

The average age at diagnosis of breast cancer was 48 (standard deviation, SD = 2.8), ranging from 43-52, with a median of 48.5 and a mode of 45 years.⁷ It was found that the average age of diagnosis of breast cancer was 45.4 (SD = 4.8), ranging from 40-54.5 range, with a median of 44.5 years.⁷
The proportion of patients under 50 years of age has been reported to be 65.5% (SD = 11) (ranging from 49-78%, with a median = 66%).⁷

Natural history and risk factors

Breast cancer shows substantial interpatient variability and has a slow growth rate compared to other cancers. The long preclinical period of breast cancer enables early detection and treatment. Patients who receive conventional treatment for metastatic disease have a median survival of more than 2 years.⁸

Several risk factors for developing breast cancer have been identified in epidemiologic studies besides female gender. Nevertheless, roughly half of all cases of breast cancer is detected in women with no identifiable risk factors beyond being female and aging.^9,10

The main risk factors are age, family history of breast cancer, prior personal history of breast cancer, increased estrogenic exposure, early menarche, late menopause, hormone replacement therapy/oral contraceptives, nulliparity, first pregnancy after age 30, diet and lifestyle (obesity, excessive alcohol consumption), radiation exposure before age 40, prior benign or premalignant breast changes, in situ cancer, atypical hyperplasia, or radial scar.⁵

Screening and inspection

Recommendations for early detection and screening of breast cancer for asymptomatic women with moderate risk include monthly breast self-examination for all women beginning at age 20; clinical breast exam for women whose age is between 20 and 39 every 3 years and yearly subsequently; and an annual mammogram starting at age 40.¹¹

Females with high familial risk for developing breast cancer or BRCA 1/2-positive patients should have an annual mammogram starting 5 years before the age when the youngest relative with breast cancer was diagnosed.¹²

Skin dimpling is one of the very important signs that needs attention in addition to nipple inversion, or architectural distortion that can signify a cancer deeper within the breast and may be obvious if the patient contracts the pectoralis muscles while pressing the palms together above her head. Preferably the breast should be softly palpated while the patient is sitting.¹³

Breast palpation

Breast tissue should be inspected with the hand held flat while the patient is resting flat with arms above her head. The breast should be systematically assessed using the palmar surfaces of the second, third, and fourth fingers, rather than the fingertips. Assessment of the tail of the breast, which extends high in the axilla, is especially important.^14,15

Regional node assessment

Clinical assessment of axillary nodes is often inaccurate. Palpable nodes can be recognised in more than 25% of patients with no clinically significant breast or other disease, and can reach up to 40% of patients with breast cancer who have clinically normal axillary nodes and have axillary nodal metastases.¹⁶

Screening mammography

Screening mammography has been shown to reduce breast cancer mortality by up to 30% among women in their 50s, and by 18% among women in their 40s.

Figure 2: The American Cancer Society guidelines for screening mammography.^17,18

Signs and symptoms at presentation

While the use of mammography is growing, more than two thirds of all breast cancers are still detected as a result of symptoms, most frequently a painless mass. Nevertheless, around 10% of patients present with breast pain and no mass. Lesser common warning signals include nipple discharge, nipple erosion or ulceration, diffuse erythema of the breast, axillary adenopathy, and symptoms associated with distant metastases.¹⁹

Suspicious palpable and mammographically detected breast lesions are diagnosed by excisional biopsy, core-cutting needle biopsy, and fine-needle aspiration (FNA). The last two techniques are in-office procedures, while excisional biopsy is usually an outpatient procedure performed with local anaesthesia. The biopsy technique depends on the size and characteristics of the mass.¹⁰

Fine-needle aspiration biopsy

Fine-needle biopsy is currently getting increasingly used since it is easy to perform and enables rapid diagnosis. Under radiological guidance, a needle is inserted into the tumour and cells are aspirated. Since fine-needle biopsy cannot discriminate in situ from invasive cancers, a needle core, incisional, or excisional biopsy is better to be used to confirm diagnosis.²⁰

Pathology

Non-invasive breast lesions are different from invasive breast lesions in that they do not invade through the basement membrane into the surrounding stroma. They are, therefore, known as carcinoma in situ. Invasive breast cancers represent a heterogeneous group of lesions with very different prognoses.²¹

TNM stage grouping

The AJCC system is a clinical/ pathologic staging scheme built on the TNM system. T denotes to tumour, N to nodes, and M to metastasis.²²

HER-2/neu Overexpression

The HER-2/neu proto-oncogene is very popular for its prognostic value. Around 25% to 30% of all breast cancer patients overexpress HER-2/neu. These patients, whether node-negative or node-positive, have been found to have a substantial decrease in 5-year survival rates.²³

DNA synthesis, cell growth, anchorage-dependent growth, tumorigenicity, and metastatic In vitro studies have shown that HER-2/neu overexpression increases potential in human breast epithelial cells.²⁴

Conclusion

Breast cancer is one of the most frequent cancers worldwide, and incidence rates are high. Several risk factors for developing breast cancer have been identified, age is the utmost significant risk factor for breast cancer. Recommendations for early detection and screening of breast cancer for asymptomatic women with moderate risk include monthly breast self-examination for all women beginning at age 20. Females with high familial risk for developing breast cancer or BRCA 1/2-positive patients should have an annual mammogram starting 5 years before the age when the youngest relative with breast cancer was diagnosed.

The average age for breast cancer in Arab countries seems a decade earlier than the average in western countries. This has important implications for screening and cancer management strategies, including the ideal age at which to begin. Adopting Western guidelines without adjustment in planning for breast cancer will waste resources without achieving the desired results.