Reproductive and Hormonal Risk Factors for Ductal Carcinoma In situ of the Breast

Abstract

One-fifth of all newly diagnosed breast cancer cases are ductal carcinoma in situ (DCIS), but little is known about DCIS risk factors. Recent studies suggest that some subtypes of DCIS (high grade, or comedo) share histopathologic and epidemiologic characteristics with invasive disease, while others (medium or low grade, or non-comedo) show different patterns. To investigate whether reproductive and hormonal risk factors differ among comedo and non-comedo types of DCIS and invasive breast cancer, we used a population-based case-control study of 1808 invasive and 446 DCIS breast cancer cases and their age and race frequency-matched controls (1564 invasive and 458 DCIS). Three or more full-term pregnancies showed a strong inverse association with comedo-type DCIS (odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.30, 0.95) and a weaker inverse association for non-comedo DCIS (OR = 0.73, 95% CI = 0.42, 1.27). Several risk factors (age at first full-term pregnancy, breastfeeding, and age at menopause) demonstrated similar associations for comedo-type DCIS and invasive breast cancer, but different associations for non-comedo DCIS. Ten or more years of oral contraceptive showed a positive association with comedo-type DCIS (OR = 1.31, 05% CI 0.70, 2.47) and invasive breast cancer (OR = 2.33, 95% CI 1.06, 5.09), but an inverse association for noncomedo DCIS (OR = 0.51, 95% CI 0.25-1.04). Our results support the theory that comedo-type DCIS may share hormonal and reproductive risk factors with invasive breast cancer, while the etiology of non-comedo DCIS deserves further investigation.

Epidemiology of Ductal Carcinoma In Situ

“…Two studies have shown an inverse association with three or more full-term pregnancies and comedo-type DCIS and a positive association with late age at first birth, similar to associations observed with invasive breast cancer, whereas non-comedo type DCIS has not been shown to be associated with reproductive risk factors (19,25). Further research is needed to examine whether genetic and nongenetic risk factors associated with invasive breast cancer are associated differently with various types of DCIS.…”

Postmenopausal Hormone Therapy is Associated with in Situ Breast Cancer Risk

“…Fourteen studies (Brinton et al, 1986;Schairer et al, 1994;Stanford et al, 1995;Longnecker et al, 1996;Henrich et al, 1998;Gapstur et al, 1999;Ross et al, 2000;Trentham-Dietz et al, 2000;Kerlikowske et al, 2003;Reeves et al, 2006;Reinier et al, 2007;Phillips et al, 2009;Calvocoressi et al, 2012;Reeves et al, 2012) used newly diagnosed BCIS as a case definition and were controlled for potential confounding factors (at least for age), through matching or adjustments.…”

“…The majority reported on nonspecific BCIS (Brinton et al, 1986;Schairer et al, 1994;Stanford et al, 1995;Henrich et al, 1998;Ross et al, 2000;Chlebowski et al, 2003;Lyytinen et al, 2006;Reinier et al, 2007;Lyytinen et al, 2009), whereas others reported on DCIS (Gapstur et al, 1999;Kerlikowske et al, 2003;Reeves et al, 2006;Phillips et al, 2009;Reeves et al, 2012) or LCIS (Trentham-Dietz et al, 2000;Reeves et al, 2006) separately. Because there is some evidence that HT may be more strongly associated with lobular than ductal lesions in invasive disease (Daling et al, 2002;Biglia et al, 2005;Phipps et al, 2010), and in situ cancers (Reeves et al, 2006), reporting on BCIS without examining specific histology may have missed important distinctions.…”

“…Because there is some evidence that HT may be more strongly associated with lobular than ductal lesions in invasive disease (Daling et al, 2002;Biglia et al, 2005;Phipps et al, 2010), and in situ cancers (Reeves et al, 2006), reporting on BCIS without examining specific histology may have missed important distinctions. A recent study by Phillips and colleagues (Phillips et al, 2009) is, to our knowledge, the first to examine HT use in relation to comedo and non-comedo DCIS, in addition to examining the effect on DCIS overall (shown in Table 1) and on invasive breast cancer. Among the subset of postmenopausal women in that study, the impact of HT on DCIS did not differ by DCIS subtype, but numbers of women in each group were small.…”

“…Most studies used home interview (Brinton et al, 1986;Longnecker et al, 1996;Ross et al, 2000) or in-person interviews (Stanford et al, 1995;Phillips et al, 2009) or telephone interviews (Schairer et al, 1994;Trentham-Dietz et al, 2000;Calvocoressi et al, 2012) or mailed questionnaires (Schairer et al, 1994;Gapstur et al, 1999;Reeves et al, 2006) that rely on the subject's ability to recall, which has repeatedly been shown to be relatively poor for hormone use. Fewer studies (Henrich et al, 1998;Kerlikowske et al, 2003;Reinier et al, 2007) used Screening mammogram questionnaire that provide detailed information on dates of use and types of drugs used.…”