Locally Advanced Breast Cancer – Strategies for Developing Nations

Worldwide, cancer incidence and cancerrelated deaths are steadily rising. According to the International Agency for Research on Cancer, new cancer cases rose from 12.7 million in 2008 to 14.1 million in 2012 (1). Similarly, 7.6 million cancerrelated deaths occurred in 2008 compared to 8.2 million in 2012. A significant proportion of these cases are attributed to breast cancer, the predominant malignancy affecting women worldwide. Since 2008, breast cancer incidence has increased by over 20% and breast cancer deaths have risen by 14% (1). Although the incidence of breast cancer is still highest in developed countries, women in developing nations are disproportionately dying as a result of this disease. Six of the 10 countries with the highest breast cancer mortality rate are lowto middle-income countries (LMICs) (Figure 1). Moreover, breast cancer in LMICs often presents when locally advanced breast cancer (LABC) (2–4) that can be easily appreciated at physical exam but is still limited to the breast and draining lymph nodes, without clinical evidence of metastatic spread. LABC is defined as tumors: (1) more than 5 cm in diameter, (2) involve the skin or the underlying pectoral muscles, (3) involve axillary, supraclavicular, and/or infraclavicular lymph nodes, or (4) inflammatory breast cancer. Despite being confined to the breast and regional nodes, locally advanced stage often heralds the rapid onset of metastatic disease, explaining high mortality rates. Solutions are needed to address this health issue. We propose practical strategies to improve the early detection of breast cancer and the treatment of LABC within developing nations. DETECTION In developed countries, national screening programs have been widely implemented. Although there are tangible benefits to mammographic screening, following the same paradigm in developing nations may not be ideal or feasible. First, women in several developing nations are diagnosed at a younger age than their counterparts in developed countries. In the United States, the median age at diagnosis is 61 years old. In comparison, the median age at diagnosis is 50 years old among women in Mexico (5) and 46 years old among Egyptian women (6). The sensitivity of mammography is affected by several factors including age and breast tissue density. In women <50 years old, the sensitivity of mammography can be as low as 68% (7). Digital mammography improves the detection of cancer in younger women but is associated with higher costs compared to film mammography. In a study of over 40,000 women, the accuracy of digital mammography was significantly higher than that of film mammography for women under 50 years old, preand peri-menopausal women and those with heterogeneously dense or extremely dense breasts on mammography (8). Screening mammograms are performed in women without symptoms of breast cancer. Diagnostic mammograms are used to diagnose breast cancer once suspicious findings have been noted on screening mammogram or if an individual has symptoms suggestive of breast cancer. Diagnostic mammograms involve more views of the breast and take longer to perform. In addition, a radiologist is present to immediately interpret the exam. When used for screening or diagnostic purposes, digital mammograms cost $11 or $33 more per examination, respectively (9). Restricting the use of digital mammograms to women under 50 years, those most likely to benefit from a more accurate assessment of breast densities, would still prove too expensive for lowto middleincome nations. According to the World Health Organization, a cost-effective health intervention is one to three times a country’s gross domestic product (GDP) per capita. Age-targeted digital mammography would cost $26,500 per quality-adjusted life year (QALY) (10), well above the costeffective threshold for most LMICs. For developing nations, screening mammography programs are likely costprohibitive with questionable benefits. This is especially true in populations with a significant number of young breast cancer patients, for whom mammography is less likely to detect malignancies and leads to more false-positive results (11– 13). It would be unwise for nations with limited resources to indiscriminately adopt the same screening strategy. Financial resources are likely better invested in public awareness campaigns and training community health workers to educate the public and perform clinical breast exams (CBE) (2, 14, 15). For example, a cost-effectiveness analysis of breast cancer interventions in Ghana revealed that mammographic screening of women 40– 69 years old would cost $12,908 per disability adjusted life year (DALY) averted. In contrast, biennial CBE and mass media awareness campaigns would cost $1299 and $1364 per DALY averted, respectively (16). Distrust of the medical system and myths about breast cancer persist, leading women