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Breast cancer early detection and resources: Where in the world do we start?

2012; Elsevier BV; Volume: 21; Issue: 4 Linguagem: Inglês

10.1016/j.breast.2012.06.007

1532-3080

Nagi S. El Saghir, Benjamin O. Anderson,

Cervical Cancer and HPV Research

As the world's most common cancer among women, and the most likely reason that a woman will die of cancer around the globe, breast cancer affects countries of all economic levels. Despite the common misconception that breast cancer is primarily a problem of high income countries, the majority of the 425,000 breast cancer deaths in 2010 occurred in developing countries. The number of young lives lost is even more disproportionately distributed. In 2010, breast cancer killed 68,000 women aged 15–49 years in developing countries versus 26,000 in developed countries. If cancer will seriously be addressed as a global health issue, then breast cancer in low and middle income countries (LMCs) cannot be ignored.1Forouzanfar M.H. Foreman K.J. Delossantos A.M. Lozano R. Lopez A.D. Murray C.J.L. et al.Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis.Lancet. 2011; 378: 1461-1484Abstract Full Text Full Text PDF PubMed Scopus (776) Google Scholar Nonetheless, decision-making regarding how to improve outcome has been a source of contentious debate for at least two decades, especially in relation to breast cancer screening and early detection. In their review article on breast cancer early detection methods for LMCs published in the current issue of The Breast, Corbex and colleagues advise against screening mammography in these low-resource settings.2Corbex M. Burton R. Sancho-Garnier H. Breast cancer early detection methods for low and middle income countries, a review of the evidence.The Breast. 2012; 21: 428-434Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar While we agree that population-based screening mammography has limited application in LMCs, we disagree with the authors' perspective that mammographic screening is a failed tool based on over-diagnosis and over-treatment. To the contrary, we believe that screening mammography has been highly successful in high-income settings, but that its application requires an infrastructure generally lacking in LMCs, and it is for this latter reason that other alternatives should be considered. The screening mammography debate has raged for more than two decades but has remained largely unchanged, despite the plethora of prospective, randomized data which repeatedly and consistently has shown a mortality benefit to the use of this tool. The screening mammography argument is repeatedly rehashed as investigators select studies that reinforce their position in either the "pro-mammography" or "anti-mammography" camps. Each side claims their perspective to be the correct "evidence-based" approach, although the argument appears to be framed more around data selection rather than overall study outcome. A philosophical argument between two scientific disciplines has emerged where public health scientists and clinical specialists seem to be locked in an epic battle defined more by perspective than unbiased review. Those investigators who do not favor mammographic screening will use population-based analyses that focus on simple, measurable outcomes such as mortality but may overlook the morbidity of treatment which becomes increasingly morbid and less successful with advanced-staged disease. For mammography detractors, the focus becomes the number of imaging studies needed to save a life, the fraction of false-positives studies, the need for additional procedures, and the emotional trauma associated with the screening process. Little or no assessment is made of the impact of cancer treatment after diagnosis, where mastectomy is more likely, systemic chemotherapy more commonly indicated and treatment more expensive, and in many LMCs, potentially unavailable. Anti-mammography dissenters typically avoid the point that 1) screening mammography is the only early detection tool proven through prospective randomized trials to decrease breast cancer mortality, and 2) the only countries that have demonstrated decreasing age-adjusted breast cancer mortality rates have adopted screening mammography as a tool for down-staging disease. By contrast, mammography advocates consider more carefully the perspective of the individual patient and downplays the impact on the population as a whole. Mammography advocates argue that with few exceptions that can be attributed to potential methodological error, randomized trials have shown mortality benefit with screening. Improved case-fatality statistics are seen in patients diagnosed with cancer when that cancer was screen detected in comparison to those that have progressed to become clinically detectable. The pro-mammography crowd tends to minimize the limitations of screening tool and the morbidity of false-positive studies, pointing out that no alternatives to screening mammography have shown survival benefit other than advanced treatment. Mammography advocates consider it inappropriate and judgmental for thoughtful scientists to overlook mortality benefit of screening mammography in lieu of false-positive examinations which are manageable and are never fatal. In 2009, the U.S. Preventive Services Task Force (USPSTF) issued guidelines that to a degree reversed the recommendations of the prior USPSTF in 2002. The new USPSTF recommended that screening mammography begin at age 50, be used every two years (rather than annually) in women ages 50–69, and that screening should be used on an individual basis rather than as a "standard test" for women 40–49 years of age.3US Preventive Services Task Force Screening for breast cancer: U.S. preventive services task force recommendation statement.Ann Intern Med. 2009 Nov 17; 151 (W-236. Erratum in: Ann Intern Med. 2010 May 18;152(10):688. Ann Intern Med. 2010 Feb 2;152(3):199-200): 716-726Crossref PubMed Scopus (0) Google Scholar The report acknowledges that screening mammography provides an approximately 15% mortality benefit to all ages, including women 40–49 years old. Nonetheless, the USPSTF concluded that this mortality benefit was outweighed by other factors largely related to the morbidity of screening false-positive results. The USPSTF suggests that the benefits of screening be carefully weighed against the potential adverse consequences and that time has come for a serious rethink of the benefits versus harms of mammography screening.3US Preventive Services Task Force Screening for breast cancer: U.S. preventive services task force recommendation statement.Ann Intern Med. 2009 Nov 17; 151 (W-236. Erratum in: Ann Intern Med. 2010 May 18;152(10):688. Ann Intern Med. 2010 Feb 2;152(3):199-200): 716-726Crossref PubMed Scopus (0) Google Scholar These USPSTF recommendations were received with disbelief and hostility in the U.S. by most cancer specialty medical groups. Critics noted that USPSTF conclusions were based primarily on statistical models, particularly when they extended the screening interval from one to two years, that USPSTF overestimated risks and underestimated benefits4Hendrick R.E. Helvie M.A. United States preventive services task force screening mammography recommendations: science ignored.Am J Roentgenol. 2011; 196: 112-116Crossref Scopus (142) Google Scholar or that the USPSTF recommendations overlooked the strongest scientific evidence, making judgments regarding data quality without consideration for the full clinical impact of the decisions.4Hendrick R.E. Helvie M.A. United States preventive services task force screening mammography recommendations: science ignored.Am J Roentgenol. 2011; 196: 112-116Crossref Scopus (142) Google Scholar, 5Kopans D.B. The 2009 US preventive services task force (USPSTF) guidelines are not supported by science: the scientific support for mammography screening.Radiol Clin North Am. 2010 Sep; 48 (Review): 843-857Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar Others argue that mammographic screening in women aged 40–49 detected smaller tumors with less nodal metastasis.6Shen N. Hammonds L.S. Madsen D. Dale P. Mammography in 40-year-old women: what difference does it make? The potential impact of the U.S. preventative services task force (USPSTF) mammography guidelines.Ann Surg Oncol. 2011 Oct; 18 ([Epub 2011 Aug 24]): 3066-3071Crossref PubMed Scopus (17) Google Scholar Notably, the USPSTF panel did not include cancer specialists such as radiologists on their panel, which itself represents a selection bias, and allows the panel to make what objectively is an arbitrary decision regarding what level of mortality benefit is needed before the findings are deemed significant. Economic subset analysis was not performed by the USPSTF to determine its selective effect on different economic and racial groups. For example, one study examined all women screened between 2004 and 2008 in California and argued that USPSTF recommendations would disproportionately impact Hispanic, Asian/Pacific Islander, and non-Hispanic black women and showed that nearly one quarter of women in California with early breast cancer likely to be screen detected, are in the 40-49 age group and would be excluded from screening and that they would be significantly affected by the potential diagnostic delays resulting from these recommendations7Aragon R. Morgan J. Wong J.H. Lum S. Potential impact of USPSTF recommendations on early diagnosis of breast cancer.Ann Surg Oncol. 2011; 18: 3137-3142Crossref PubMed Scopus (13) Google Scholar The American Cancer Society continues to endorse mammography screening, annually, starting age 408Smith R.A. Cokkinides V. Brawley O.W. Cancer screening in the United States, 2012: a review of current American cancer society guidelines and current issues in cancer screening.CA Cancer J Clin. 2012; 62: 129-142Crossref Scopus (126) Google Scholar in addition to annual clinical breast examination (CBE), but dropped breast self-examination (BSE) as a screening tool. The full scope of this discussion goes beyond what can be reviewed in this editorial, but if nothing else, it shows that different groups of sound mind and good scientific background can come to different conclusions based on the same evidence. Corbex and colleagues use the USPSTF recommendations to argue against screening mammography in LMCs at any level, an extrapolation that was not endorsed by the USPSTF itself. Corbex argues that the benefits of screening mammography are likely to be low or even null because the incidence of breast cancer in LMCs is much lower than in the Western countries and that the peak of incidence is younger and that optimum participation rates will be difficult to reach. They argue that the cost associated with mammographic screening programs is high enough (buying new machines, training radiologists and radiographers, organizing population invitation and follow-up, maintaining a screening register, treating positive patients, etc) to make the benefit/cost ratio unacceptable for most LMC.2Corbex M. Burton R. Sancho-Garnier H. Breast cancer early detection methods for low and middle income countries, a review of the evidence.The Breast. 2012; 21: 428-434Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar The points are well taken, and do suggest that other steps should be taken in these settings where the implementation of screening mammography is impractical or unaffordable. But in contrast to Corbex and colleagues, we argue that screening mammography continues to play a key role in addressing breast cancer as a global issue, but that there are both economic and structural prerequisites before its benefits can be achieved. The discussion about mammographic screening's strengths, limitations, frequency and target age group, which has relevance to high income countries with established healthcare infrastructures, has overshadowed more practical questions for addressing breast cancer outcomes in LMCs. Throughout the world, women in developing countries are most often first diagnosed with locally advanced (Stage III) or metastatic (Stage IV) cancer.9Chopra R. The Indian scene.J Clin Oncol. 2001 Sep 15; 19: 106S-111SPubMed Google Scholar, 10El-Saghir N.S. Khalil M. Eid T. El Kinge A.R. Charafeddine M. Geara F. et al.Trends in epidemiology and management of breast cancer in developing Arab countries: a literature and registry analysis.Int J Surg. 2007; 5: 225-233Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar In the majority of LMCs, 50–80% of breast cancer is still diagnosed at advanced stages which, along with the lack of availability of radiation therapy centers within proximity of the patient and treating physician, makes that mastectomy (without reconstruction) the most commonly performed surgical procedure for breast cancer in patients of whom 50% are below the age of 50 in LMCs.10El-Saghir N.S. Khalil M. Eid T. El Kinge A.R. Charafeddine M. Geara F. et al.Trends in epidemiology and management of breast cancer in developing Arab countries: a literature and registry analysis.Int J Surg. 2007; 5: 225-233Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar, 11Yip C.H. Cazap E. Anderson B.O. Bright K.L. Caleffi M. Cardoso F. et al.Breast cancer management in middle-resource countries (MRCs): consensus statement from the breast health global initiative.Breast. 2011 Apr; 20: S12-S19Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 12El Saghir N.S. Adebamowo C.A. Anderson B.O. Carlson R.W. Bird P.A. Corbex M. et al.Breast cancer management in low resource countries (LRCs): consensus statement from the breast health global initiative.Breast. 2011 Apr; 20: S3-11Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar These large palpable, visible or ulcerated cancers are easily detected on inspection and clinical examination, obviating the value of screen detection. Advanced cancers are more expensive to treat, less likely to respond to therapy, and most often prove incurable in any healthcare setting. The critical questions, then, must not revolve around mammographic availability in LMCs, but instead should focus on interventions whereby cancers can be diagnosed at less advanced stages, so-called "clinical down-staging," followed by adequate loco-regional and systemic treatments. The argument that BSE and CBE have not been shown in randomized trials to improve breast cancer outcome must be weighed against the fact that both awareness of the patient regarding changes in her breast is a mandatory aspect of any breast cancer program. It is argued that neither of the major BSE screening trials showed a mortality benefit. Regarding the Shanghai BSE randomized trial, there was in retrospect limited room for BSE screening to achieve a mortality reduction since BC awareness in the population was already high and clinical stage at diagnosis was relatively good: In the Shanghai trial 45% of the control women were Stage I and only 1.5% of the BSE intervention and 2.5% of the control women were Stage IV13Thomas D.B. Gao D.L. Ray R.M. Wang W.W. Allison C.J. Chen F.L. et al.Randomized trial of breast self-examination in Shanghai: final results.J Natl Cancer Inst. 2002 Oct 2; 94: 1445-1457Crossref PubMed Scopus (560) Google Scholar. This trial results demonstrated that BSE does not carry benefit in such settings. The question remains open for settings where the majority of cancers are diagnosed at stages III or IV. A randomized BSE trial in a LMC where most of the patients present at stage III or IV would be of great value in this context. Clinical Breast Examination (CBE) is recommended as part of periodic physical examination every three years between 20 and 30 then yearly afterwards.8Smith R.A. Cokkinides V. Brawley O.W. Cancer screening in the United States, 2012: a review of current American cancer society guidelines and current issues in cancer screening.CA Cancer J Clin. 2012; 62: 129-142Crossref Scopus (126) Google Scholar This remains an important issue to emphasize because in many parts of the world, because of shyness and traditional perceptions, breast examination is not done routinely. However, experience tells us that even in the most conservative societies, when women are offered to have a breast examination, they tend to accept it, especially if the examining physician is a female, or in the presence of a female nurse. Hands-on teaching women how to perform proper BSE by female nurses and social workers helps to detect breast cancer at early stages.14Boulos S. Gadallah M. Neguib S. Essam E. Youssef A. Costa A. et al.Breast screening in the emerging world: high prevalence of breast cancer in Cairo.Breast. 2005; 14: 340-346Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 15Salem D. Kamal R. Helal M. Hamed S.T. Abdelrazek N.A. Said N.H. et al.Women health Outreach program; a new experience for all Egyptian women.J Egypt Nat Cancer Inst. 2008; 20: 313-322PubMed Google Scholar, 16El Saghir N.S. Responding to the challenges of breast cancer in Egypt and other Arab countries (editorial).J Egypt Natl Cancer Inst. 2008; 20: 309-312PubMed Google Scholar While legitimate questions remain regarding the role of CBE as a "screening tool", research studies to date generally present an excessively limited perspective of CBE as a clinical intervention. It is not possible to evaluate and treat breast cancer without CBE, since surgical evaluation and execution depends on it. There is an undeniable need for any clinical system to have providers who have some level of competence in CBE. In the absence of screening, CBE is the basis for selecting patients for evaluation and work-up. CBE is the basis for deciding which patients will be sent from their village to the medical facility where work-ups can be performed. Arguing about the value of CBE is a bit like arguing about the value of a scalpel – we may not have a study demonstrating that the scalpel reduces breast cancer mortality, but breast surgery cannot be performed in its absence. CBE, like scalpels, is a basic level tool. The strength of the Corbex review relates to their summary of the methodology for clinical down-staging of breast cancer based on the WHO-EMRO regional strategy.17WHO EMRO starategy for cancer control; 2008.Google Scholar New studies should be focused on pragmatic implementation of down-staging programs featuring CBE as the initial intervention, rather than arguing ad infinitum about a screening tool that cannot be implemented in most of the world. Healthcare leaders should ask questions about how countries with limited resources can get themselves to the place where screening mammography is a legitimate question. Countries where the median tumor size is 4 or 5 cm and where women commonly present with ulcerated advanced tumors do not benefit from our discussion about screening mammography. They need solutions that are ready for implementation today with existing resources. Improvement of mortality and reduction of morbidity from breast cancer in LMCs must be achieved by down-staging breast cancer at diagnosis. Discovering breast cancer at earlier stages is achievable by raising awareness, teaching BSE, promoting CBE, and screening mammography when they become able to afford it and have the infrastructure to do it. Current awareness campaigns will pave the way for it. Awareness programs are contributing to better diagnosis, early detection of breast cancer at earlier stages, hence saving breast and saving lives and these in the long run are cost-saving and save resources. The Breast Health Global Initiative (BHGI) recommends Awareness, BSE, CBE, screening mammography for a target population in some high-middle income countries for a target population 50–69, and acknowledged that while women 40–49 represent a significant proportion of women with breast cancer in LMIC, probably because of young aged populations, applying screening mammography to them may be costly and requires lots of quality control measures to avoidance unnecessary investigations and procedures; BHGI recommends increased awareness campaigns, SBE and BCE for this younger age group.18Anderson B.O. Cazap E. El Saghir N.S. Yip C.H. Khaled H.M. Otero I.V. et al.Optimisation of breast cancer management in low-resource and middle-resource countries: executive summary of the breast health global initiative consensus, 2010.Lancet Oncol. 2011; 12: 387-398Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar Such attitudes go along with "Do what you can" recommendation made at the BHGI Summit in Chicago, Illinois, USA in June 2010 and published in 2011.19Harford J.B. Breast-cancer early detection in low-income and middle-income countries: do what you can versus one size fits all.Lancet Oncol. 2011 Mar; 12: 306-312Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar Is it not time to stop arguing about whether the glass is half-empty or half-full? Instead, we should address the needs of women in LMCs stricken with breast cancer rather than being paralyzed into inaction. Instead of debating whether or not mammography "works", which the randomized trials have already established when it is used in the correct setting and with proper patient selection, we should consider how countries not yet ready for mammography can prepare themselves for the predictable breast cancer epidemic, and how they should prevent it by clinical down-staging, implementing better management and setting up infrastructure for early detection.