In most low- and middle-resource countries (LMCs), breast cancer incidence rates are increasing more rapidly than in regions where incidence rates already are high. Despite the younger age structure of most developing countries, LMCs already account for 45% of the incident breast cancer cases and cause 54% of the annual breast cancer deaths around the globe.1 Even assuming (conservatively) that there will be no change in underlying age-specific rates, a nearly 50% increase is anticipated in breast cancer global incidence and mortality between the years 2002 and 2020 caused simply by the aging of current global populations. These rising cancer rates will be disproportionately greater among countries in the developing world, and the rates in LMCs are projected to reach a 55% increased incidence and a 58% increased mortality in <20 years.1 In reality, these projected statistics probably underestimate future cancer rates, because the few data available from LMCs reveal increasing age-specific breast cancer incidence and mortality rates, especially among recent birth cohorts. This is especially true for urban women in LMCs and is attributable in part to the adoption of Western lifestyles.2, 3
Improvements in breast cancer survival in the industrialized world that have been observed in recent decades can be attributed to early detection by screening combined with timely and effective treatment as guided by the results of extensive and rigorously performed clinical trials.4 Randomized trials of screening mammography combined with clinical breast examination (CBE) initiated in the 1970s demonstrated that early cancer detection within a given population leads to down-staging of disease and improvement in breast cancer survival. At the same time, randomized trials of systemic therapies for breast cancer proved that endocrine therapy for estrogen receptor (ER)-positive cancers and cytotoxic chemotherapy for ER-negative cancers improve survival and produce durable long-term cure among patients with lymph node negative, lymph node positive, and even locally advanced breast cancers.5 Breast cancer mortality essentially was unchanged in the United States for 6 decades between 1930 and 1990. By contrast, since 1990, age-adjusted breast cancer mortality has been dropping by nearly 2% each year in the United States, indicating that true progress is being made in the management of this disease.6 Similar improvements also are being observed in Western European countries that have invoked population-wide early detection and adjuvant treatment programs.
Notably, minority women in the United States are more likely to present with advanced stage disease and have higher mortality rates than white women, although white women and black women who present with similar stage disease and receive similar treatment have similar outcomes. These findings suggest that differences in stage at presentation should represent a primary target for research, the goal of which is to determine which interventions best reduce disparities in cancer outcomes among women from different social or racial groups.7
In LMCs, worsened cancer survival is attributable largely to late-stage presentation, which leads to particularly poor outcomes when coupled with limited diagnostic and treatment capacity.8 Of the >75,000 patients with newly diagnosed breast cancer who present for treatment each year in India, between 50% and 70% have locally advanced disease at diagnosis.9 By comparison, 38% of European patients with breast cancer and only 30% of American patients with breast cancer reportedly had locally advanced cancer at diagnosis in the early 1990s.10 Thus, identifying the factors that promote or inhibit women's participation in early detection programs becomes highly relevant to the relative success of a population-based cancer strategy.
Public awareness that breast cancer outcomes are improved through early detection is critical to improving participation in early detection programs, whether these programs are based on CBE, screening mammography, or some other hybrid of early detection strategies. Early detection programs can be challenging to implement successfully in LMCs, because the general population may be uneducated about breast cancer or may have major misconceptions about the nature or curability of the disease.11 Nonetheless, the majority of patients who are diagnosed correctly and treated properly for early stage breast cancer will live on to become survivors of the disease. Organized breast cancer survivor groups like Reach for Recovery play a vital role in providing newly diagnosed women with practical and emotional support through cancer treatment and beyond.12 Survivor groups also can organize into political advocacy groups that have a real and positive impact on healthcare policy or national cancer research agendas.13, 14 Ultimately, breast cancer survivors become the most important communicators regarding the relevance and impact of early detection, and their very existence becomes proof to the general population that favorable cancer outcomes are possible.
Social or cultural issues may have an adverse impact on women's participation in early detection programs. Failure to anticipate these inhibitory factors can adversely affect research or clinical outcomes. For example, a large, population-based, randomized trial that studied screening CBE in the Philippines could not be completed, because >60% of women from this relatively well educated population in Manila refused to complete the required follow-up diagnostic studies once a finding on CBE was identified. The researchers concluded that cultural and logistic barriers to seeking diagnosis and treatment must be addressed before any screening program is introduced.15
In this issue of Cancer, Azaiza et al have provided an important analysis of screening behaviors in relation to cultural and environmental barriers among women who live in the Palestinian Authority.16 This highly relevant study indicated that women in this region of the Middle East were more likely to undergo screening mammography if they 1) were less religious, 2) described having fewer personal barriers to examinations, and 3) indicated a lower degree of cancer fatalism. Women who consented to CBE had a higher perceived effectiveness of CBE and described lower levels of cancer fatalism. Muslim women were half as likely as Christian women to participate in CBE screening. Similar to women who underwent CBE, women were more likely to perform self-breast examination (SBE) if they were more highly educated, resided in cities, were Christian, and were less religious. Also, women who had a first-degree relative with breast cancer were more likely to practice SBE.
Fatalism can create a very significant obstacle for participation in early detection programs. Individuals who believe that illness is determined by the Fates may not be empowered to act in ways that prevent disease. This study of women from the Palestinian Authority suggests that fatalistic belief systems may be more common among women who consider themselves more religious. One approach to improved participation in breast cancer screening may be to recruit church or religious leaders as spokespersons for early detection messages. When religious practices require women to remain completely covered, as is the case in many Muslim countries, women may believe that SBE and CBE are unacceptable or shameful practices. Special screening clinics staffed by women physicians and nurses and adapted to the needs of specific religious communities may be required to promote screening participation in these regions of the world.
The value of SBE as a screening tool in LMCs remains an area of controversy. Some groups have concluded that self-examination has no benefit in improving breast cancer outcome based primarily on the negative SBE randomized trial performed in Shanghai, China and reported in October 2002.17 That well executed, cluster randomized trial assigned 260 factories to the instruction group and 259 factories to the control group. All women who were current or retired employees ages 30 to 65 years were eligible for the study. Women from the instruction factories were given intensive instruction in SBE, reinforcement sessions 1 year and 3 years later, and practiced SBE under the supervision of a factory medical worker every 6 months for 5 years. Because no difference in mortality was observed between the groups trained in SBE versus groups that were not, many concluded that SBE is not of clinical value.
In fact, the Shanghai study data do not support the sweeping conclusion that SBE is without value in non-Chinese populations. Generally overlooked from the Shanghai SBE trial is the finding that even the Chinese women in the control group from this study performed SBE quite effectively despite the lack of formal training in SBE technique. Over 40% of the breast cancers diagnosed in the Shanghai control group measured <2 cm in greatest dimension, suggesting that Chinese women appear to do well with breast cancer early detection without the assistance of training in SBE methodology. These statistics stand in strong contrast to cancer demographics from the Middle East, Africa, and India, where the median tumor size commonly is from 4 cm to 6 cm at presentation, and the majority of women present with locally advanced or metastatic breast disease at initial diagnosis.
Preliminary results from a new cluster randomized trial from Mumbai, India suggest that CBE, in fact, facilitates the down-staging of breast cancer in countries where women commonly present with advanced stage disease at diagnosis.18 Women in the intervention group from that study underwent CBE for the detection of breast abnormalities and also underwent cervical inspection for plaque or lesions that warranted cryotherapy. For comparison, women in the control group received health education alone but did not undergo CBE (or cervical inspection). Screening among the intervention group is planned to occur every 2 years for 4 cycles; then, the women will be monitored for 8 years to determine cancer outcome. Currently, >75,000 women have been randomized to each arm. In a recent update of the study and after 3 rounds of screening, more breast cancers have been diagnosed in the intervention group (125 cases vs 87 cases in the control group), and, of these, a great proportion had stage 0, I, or II disease at initial diagnosis (62% in the intervention group vs 44% in the control group).
Based on these findings, many groups (such as the National Comprehensive Cancer Network [NCCN]) continue to recommend CBE and breast self-awareness as appropriate steps for breast cancer screening and diagnosis. The NCCN guidelines recommend that 1) women should be familiar with their breasts and promptly report changes to their physician; 2) consistent, periodic SBE may be used to facilitate breast self-awareness; and 3) in premenopausal women, SBE may be most informative at the end of menses.19 Future studies should help to identify which factors are most likely to improve women's participation in breast cancer early detection programs and which techniques realistically can be used to down-stage disease, increasing the feasibility, effectiveness, and cost containment of cancer treatment in LMCs.