By using a simple seven-question instrument to inquire about the family history of cancer in women from primary health care units of an underserved region in southern Brazil, we identified a significant proportion with family histories of cancer who fulfilled criteria for one of the most commonly recognized hereditary breast cancer syndromes. The overall prevalence (6.2%) was similar to that described in other population-based samples, although only a few studies have addressed this issue to date (Pharoah et al., 2000
; Hughes et al., 2003
; Palomaki et al., 2006
). Most of the families with hereditary breast cancer phenotypes corresponded to LFL syndrome. Although there is a phenotypic overlap among the HBOC, LFS/LFL and HBCC syndromes, the high frequency of LFL pedigrees observed here is striking, especially considering that the original questionnaire used to identify these patients was not designed to screen for LFS/LFL.
Already ten years ago (Varley et al., 1999
) described certain low penetrance TP53
alleles and suggested that deleterious mutations in TP53
(or related genes) may be more frequent in the population than previously estimated. In addition, several recent reports have indicated that a deleterious germline mutation in TP53
, R337H, might be very prevalent and related to a founder effect in southern Brazil (Pinto et al., 2004
; Achatz et al.
., 2007; Palmero et al., 2008
). Although some of the criteria used here to diagnose the LFL phenotype were not stringent (i.e.
Eeles criteria used to classify LFL phenotype) and may have little sensitivity for identifying germline TP53
mutations in other countries, the unexpectedly high number of criteria-positive patients suggests that LFL may indeed be a common phenotype for hereditary breast cancer in and around Porto Alegre. Future results from germline mutation testing should help to clarify this issue and contribute to our understanding of the applicability and discriminatory capacity of breast cancer risk estimation models, current diagnostic criteria and mutation prediction models for hereditary breast cancer syndromes in this population. If such a high prevalence of LFS/LFL syndrome is confirmed among families in this geographic area, an effort will have to be made to facilitate the identification of high-risk individuals and delineate effective cancer screening and prevention programs in these subjects.
The relatively large proportion of women (72.3%) who attended the proposed GCRA was very encouraging and comparable to that encountered in similar studies, e.g.
, 88% and 70% in underserved communities in the U.S.A. (Ricker et al., 2006
) and Singapore (Chin et al., 2005
), respectively. Furthermore, in a recent study by ONeill et al.
(2006) in the U.S.A., the outcome of genetics referrals was evaluated in a group of women with estimated BRCA
mutation probabilities ≥ 10%. Within six-months after referral, 36% of the patients had undergone genetic evaluations (acceptors), 27% still intended to seek (intenders) and 36% refused such assessment (decliners). Population-based mammographic screening programs worldwide have also reported compliance rates of 61%-83% (Banks et al., 2002
; O'Malley et al., 2002
; Finney et al., 2006
In this study, the number of attenders also has to be interpreted in light of the difficulties that most of these women face to seek advice, health care and cancer prevention opportunities. First, there might be a cultural difference in cancer-associated risk perception and/or a difficulty in understanding the impact of preventive interventions. The way of dealing with risk is not only influenced by risk perception but also by culture. This was clearly demonstrated by Hofstede (1997)
in a landmark study in which different cultures around the world were characterized based on five parameters, including the uncertainty avoidance index (UAI). This index, which reflects the tolerability of a given society towards uncertainty and ambiguity, is higher in Brazil than in Denmark, the United Kingdom and the U.S.A. Such differences could interfere with cancer risk perception and motivation to seek GCRA. In addition, certain cultures are more fatalistic about cancer and perceive fewer benefits from screening (Russell et al., 2006
). Second, there may be a knowledge barrier in understanding how preventive measures will ultimately increase quality of life (Achat et al., 2005
; Ricker et al., 2006
; Farmer et al., 2007
). Third, in many of these women, care of themselves is often set aside because of more urgent needs, such as providing food, housing and education for their families. Fourth, it may be that these women are simply obeying and respecting a hierarchical structure in which they attend GCRA only because they are told to do so, and their cultural conditioning generally makes them follow health recommendations once they are given. Finally, there has been a historical lack of resources to ensure that adequate screening is provided in this area, even if there is evidence for a higher risk (Smith et al., 2006
). Consequently, most of these women may have seen the program offered here as an opportunity to be grasped since they would otherwise face significant difficulties in following standard recommendations for breast cancer screening if they relied solely upon the public health care system.
For all of these reasons, programs such as that described here, which attempt to identify and prospectively follow women with an increased risk of cancer, need to consider the importance of patient education and social interventions (i.e., facilitate transportation, nutrition and childcare) in the difficult task of maintaining compliance to the recommended guidelines. A more detailed study of non-attenders may provide better clues on how to improve coverage for programs such as these, thereby ensuring that most high-risk patients have access to the information and preventive interventions they require.
In conclusion, the implementation of a GCRA program for an underserved community in southern Brazil revealed that the overall prevalence of a hereditary breast cancer phenotype in this population-based sample of women was 6.2%, which may be a matter of considerable concern in this region. In addition, the establishment of breast cancer risk categories allowed the identification of higher risk women who may benefit from more intensive screening. The relatively high number of women who attended GCRA sessions after an initial referral suggested that the program was well accepted by the community and is feasible, regardless of potential cultural, economic and social barriers.