The present meta-analysis was conducted to investigate the subtype of BBD with high breast cancer risk and the influence of a positive family history on various subtypes of BBD. This study showed that all subtypes of BBD increased the subsequent breast cancer risk, and ALH had a highest risk. Furthermore, our results suggested that a first-degree family history increased risk in women with NP and PD. Although compared to women without family history and PD, women with a first-degree family history and AH had the highest risk; a first-degree family history did not increase risk in women with AH. Increased screening, chemoprevention, and even prophylactic surgery should be considered for women with ALH or women with a first-degree family history and AH.
Consistent with previous studies, our study showed that PDWA had a slightly increased risk (OR = 1.44, 95% CI 1.28–1.63) of breast cancer, and AH had a substantially increased risk (OR = 2.81, 95% CI 1.91–4.12). Worsham et al. (2007
) suggested that breast cancer risk from BBD for women with ADH may be higher than for women with ALH. However, the opposite results were reported in other studies (Fitzgibbons et al. 1998
; Kabat et al. 2010
; Collins et al. 2007
). This meta-analysis suggested that breast cancer risk from BBD for women with ALH (OR = 5.14, 95% CI 3.52–7.52) may be higher than for women with ADH (OR = 2.93, 95% CI 2.16-3.97). Previous study (Hartmann et al. 2005
) showed that degree of family history was an independent risk factor. The risk ratio of breast cancer for NP women with a weak family history was 1.12, but no significant difference was observed. The women with a first-degree family history were included in this study for investigating the interplay between BBD and family history of breast cancer, and the first-degree family history was a significant risk factor for women with different histological subtypes of BBD except for AH. The future large study should be carried out to evaluate the breast cancer risk for women with different degrees of family history.
Recommendations for breast cancer screening and risk-reduction options for women at average risk were different from women at high risk (Griffin and Pearlman 2010
). Routine mammography should be performed for women at average risk, but no special risk-reduction management should be done (Griffin and Pearlman 2010
; Meissner et al. 2011
). However, increased screening, chemoprevention, and prophylactic surgery should be considered for women at high risk. This meta-analysis suggested that women with AH, especially for ALH and AH combined with a first-degree family history, were at high risk, so that risk-reduction options should be considered.
Several issues may affect the efficiency of specific types of BBD with risk of breast cancer. First, the reference group used to examine the subsequent breast cancer risk among women with BBD was variant in different studies. The general population was used as reference group in some studies (Hartmann et al. 2005
; Carter et al. 1988
; McDivitt et al. 1992
; Degnim et al. 2007
), while NP was used in others (Dupont and Page 1985
; London et al. 1992
; Marshall et al. 1997
; Worsham et al. 2009
; Jacobs et al. 1999
). In this meta-analysis, NP was used as reference group for calculation although data were extracted from studies with different reference groups. Therefore, this study gave a more precise estimation of the risk from a large sample. Second, there was no pathological review in some studies (Wang et al. 2004
), and the classification of BBD was unequal in different centers (King et al. 2000
; Patterson et al. 2004
). However, the breast lesions included in this meta-analysis were all biopsy-proved BBD and reviewed by experienced pathologists.
On the other hand, some limitations still exist in this meta-analysis. First, both very old and relatively new studies were included in this study; the methodological limitation of this analysis should be considered. Second, of these ten studies, most subjects were Caucasians, including some African-Americans, while no Asians were included. Therefore, the conclusion in Asian populations was still unclear. Third, the present results were based on unadjusted ORs, and more precise estimation may be adjusted by other potential covariates.
In conclusion, this meta-analysis strongly suggested that women with AH, especially for ALH and AH combined with a first-degree family history, were at high risk. So risk-reduction options should be considered for these women. Further study with larger sample size is necessary to get more precise estimation of breast cancer risk after diagnosis of BBD.