Limits...
Mammographic density and breast cancer in women from high risk families.

Ramón Y Cajal T, Chirivella I, Miranda J, Teule A, Izquierdo Á, Balmaña J, Sánchez-Heras AB, Llort G, Fisas D, Lope V, Hernández-Agudo E, Juan-Fita MJ, Tena I, Robles L, Guillén-Ponce C, Pérez-Segura P, Luque-Molina MS, Hernando-Polo S, Salinas M, Brunet J, Salas-Trejo MD, Barnadas A, Pollán M - Breast Cancer Res. (2015)

Bottom Line: MD was associated with subsequent development BC (OR per category of MD=1.45; 95 % confidence interval=1.18-1.78, P-value<0.001), with no significant differences between BRCA1 and BRCA2 mutation carriers (P-value=0.48).Finally, no statistically significant differences were observed in the association of MD with specific BC subtypes.Our study, the largest to date on this issue, confirms that MD is an independent risk factor for all BC subtypes in either BRCA1 and BRCA2 mutation carriers, and should be considered a phenotype risk marker in this context.

View Article: PubMed Central - PubMed

Affiliation: Medical Oncology Department, Hospital Santa Creu I Sant Pau, Barcelona, Spain. TRamon@santpau.cat.

ABSTRACT

Introduction: Mammographic density (MD) is one of the strongest determinants of sporadic breast cancer (BC). In this study, we compared MD in BRCA1/2 mutation carriers and non-carriers from BRCA1/2 mutation-positive families and investigated the association between MD and BC among BRCA1/2 mutation carriers per type of mutation and tumor subtype.

Methods: The study was carried out in 1039 female members of BRCA1 and BRCA2 mutation-positive families followed at 16 Spanish Genetic Counseling Units. Participants' density was scored retrospectively from available mammograms by a single blinded radiologist using a 5-category scale (<10 %, 10-25 %, 25-50 %, 50-75 %, >75 %). In BC cases, we selected mammograms taken prior to diagnosis or from the contralateral breast, whereas, in non-cases, the last screening mammogram was evaluated. MD distribution in carriers and non-carriers was compared using ordinal logistic models, and the association between MD and BC in BRCA1/2 mutation carriers was studied using logistic regression. Huber-White robust estimators of variance were used to take into account correlations between family members. A similar multinomial model was used to explore this association by BC subtype.

Results: We identified and scored mammograms from 341 BRCA1, 350 BRCA2 mutation carriers and 229 non-carriers. Compared to non-carriers, MD was significantly lower among BRCA2 mutation carriers (odds ratio (OR) =0.71; P-value=0.04), but not among BRCA1 carriers (OR=0.84; P-value=0.33). MD was associated with subsequent development BC (OR per category of MD=1.45; 95 % confidence interval=1.18-1.78, P-value<0.001), with no significant differences between BRCA1 and BRCA2 mutation carriers (P-value=0.48). Finally, no statistically significant differences were observed in the association of MD with specific BC subtypes.

Conclusions: Our study, the largest to date on this issue, confirms that MD is an independent risk factor for all BC subtypes in either BRCA1 and BRCA2 mutation carriers, and should be considered a phenotype risk marker in this context.

No MeSH data available.


Related in: MedlinePlus

Distribution of mammographic density in breast cancer cases and non-cases in the following groups: non-carriers, BRCA1 mutation carriers and BRCA2 mutation carriers
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4499171&req=5

Fig1: Distribution of mammographic density in breast cancer cases and non-cases in the following groups: non-carriers, BRCA1 mutation carriers and BRCA2 mutation carriers

Mentions: The distribution of MD in BC cases and non-cases for women who were non-carriers and BRCA1 and BRCA2 mutation-carriers is presented in Fig. 1. Cases tended to be more frequently classified in the higher MD categories. Given the limited number of BC cases among the non-carriers group, we did not evaluate the potential different effect of MD on cancer risk in non-carriers. Table 3 shows the association between MD and subsequent development of BC among BRCA1/2 mutation carriers. After adjusting for age at mammogram, BMI, menopause (premenopause/natural menopause/surgical menopause), parity, age at first birth, HRT, type of mammogram and time of follow up, there was a clear association between MD and subsequent BC development among BRCA1/2 mutation carriers, with a statistically significant dose-response trend (P value <0.001). The OR in women with density 50−75 % relative to women with density ≤10 % was 3.24 (95 % CI = 1.43, 7.35; P value = 0.005), while women in the highest MD category, namely >75 %, had an OR of 4.34 (95 % CI = 1.71, 11.1; P value = 0.002). The association between MD and BC tended to be stronger among BRCA2 mutation carriers (OR per increase in one category of MD of 1.60 in BRCA2 and of 1.37 in BRCA1 carriers), but these differences were not statistically significant (P value for heterogeneity = 0.449). Sensitivity analysis including only the cases with a mammogram obtained at least 6 months before cancer diagnosis had comparable results (see the central columns in Table 3). Finally, given that most mammograms from BC cases were analog, the last columns present the association between MD and BC using only analog images (Table 3). ORs tended to be stronger in this case, particularly for BRCA2 mutation carriers. The analysis of digital images was hampered by the small number of BC cases available (40 cases: 6 MD <=10 %, 6 MD = 11−25 %, 17 MD = 26−50 %, 9 MD = 51−75 % and 2 MD >75 %) and no association between MD and BC was observed (ORs of 1.23, 1.94, 1.88 and 1.22, respectively; none of the ORs were statistically significant).Fig. 1


Mammographic density and breast cancer in women from high risk families.

Ramón Y Cajal T, Chirivella I, Miranda J, Teule A, Izquierdo Á, Balmaña J, Sánchez-Heras AB, Llort G, Fisas D, Lope V, Hernández-Agudo E, Juan-Fita MJ, Tena I, Robles L, Guillén-Ponce C, Pérez-Segura P, Luque-Molina MS, Hernando-Polo S, Salinas M, Brunet J, Salas-Trejo MD, Barnadas A, Pollán M - Breast Cancer Res. (2015)

Distribution of mammographic density in breast cancer cases and non-cases in the following groups: non-carriers, BRCA1 mutation carriers and BRCA2 mutation carriers
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4499171&req=5

Fig1: Distribution of mammographic density in breast cancer cases and non-cases in the following groups: non-carriers, BRCA1 mutation carriers and BRCA2 mutation carriers
Mentions: The distribution of MD in BC cases and non-cases for women who were non-carriers and BRCA1 and BRCA2 mutation-carriers is presented in Fig. 1. Cases tended to be more frequently classified in the higher MD categories. Given the limited number of BC cases among the non-carriers group, we did not evaluate the potential different effect of MD on cancer risk in non-carriers. Table 3 shows the association between MD and subsequent development of BC among BRCA1/2 mutation carriers. After adjusting for age at mammogram, BMI, menopause (premenopause/natural menopause/surgical menopause), parity, age at first birth, HRT, type of mammogram and time of follow up, there was a clear association between MD and subsequent BC development among BRCA1/2 mutation carriers, with a statistically significant dose-response trend (P value <0.001). The OR in women with density 50−75 % relative to women with density ≤10 % was 3.24 (95 % CI = 1.43, 7.35; P value = 0.005), while women in the highest MD category, namely >75 %, had an OR of 4.34 (95 % CI = 1.71, 11.1; P value = 0.002). The association between MD and BC tended to be stronger among BRCA2 mutation carriers (OR per increase in one category of MD of 1.60 in BRCA2 and of 1.37 in BRCA1 carriers), but these differences were not statistically significant (P value for heterogeneity = 0.449). Sensitivity analysis including only the cases with a mammogram obtained at least 6 months before cancer diagnosis had comparable results (see the central columns in Table 3). Finally, given that most mammograms from BC cases were analog, the last columns present the association between MD and BC using only analog images (Table 3). ORs tended to be stronger in this case, particularly for BRCA2 mutation carriers. The analysis of digital images was hampered by the small number of BC cases available (40 cases: 6 MD <=10 %, 6 MD = 11−25 %, 17 MD = 26−50 %, 9 MD = 51−75 % and 2 MD >75 %) and no association between MD and BC was observed (ORs of 1.23, 1.94, 1.88 and 1.22, respectively; none of the ORs were statistically significant).Fig. 1

Bottom Line: MD was associated with subsequent development BC (OR per category of MD=1.45; 95 % confidence interval=1.18-1.78, P-value<0.001), with no significant differences between BRCA1 and BRCA2 mutation carriers (P-value=0.48).Finally, no statistically significant differences were observed in the association of MD with specific BC subtypes.Our study, the largest to date on this issue, confirms that MD is an independent risk factor for all BC subtypes in either BRCA1 and BRCA2 mutation carriers, and should be considered a phenotype risk marker in this context.

View Article: PubMed Central - PubMed

Affiliation: Medical Oncology Department, Hospital Santa Creu I Sant Pau, Barcelona, Spain. TRamon@santpau.cat.

ABSTRACT

Introduction: Mammographic density (MD) is one of the strongest determinants of sporadic breast cancer (BC). In this study, we compared MD in BRCA1/2 mutation carriers and non-carriers from BRCA1/2 mutation-positive families and investigated the association between MD and BC among BRCA1/2 mutation carriers per type of mutation and tumor subtype.

Methods: The study was carried out in 1039 female members of BRCA1 and BRCA2 mutation-positive families followed at 16 Spanish Genetic Counseling Units. Participants' density was scored retrospectively from available mammograms by a single blinded radiologist using a 5-category scale (<10 %, 10-25 %, 25-50 %, 50-75 %, >75 %). In BC cases, we selected mammograms taken prior to diagnosis or from the contralateral breast, whereas, in non-cases, the last screening mammogram was evaluated. MD distribution in carriers and non-carriers was compared using ordinal logistic models, and the association between MD and BC in BRCA1/2 mutation carriers was studied using logistic regression. Huber-White robust estimators of variance were used to take into account correlations between family members. A similar multinomial model was used to explore this association by BC subtype.

Results: We identified and scored mammograms from 341 BRCA1, 350 BRCA2 mutation carriers and 229 non-carriers. Compared to non-carriers, MD was significantly lower among BRCA2 mutation carriers (odds ratio (OR) =0.71; P-value=0.04), but not among BRCA1 carriers (OR=0.84; P-value=0.33). MD was associated with subsequent development BC (OR per category of MD=1.45; 95 % confidence interval=1.18-1.78, P-value<0.001), with no significant differences between BRCA1 and BRCA2 mutation carriers (P-value=0.48). Finally, no statistically significant differences were observed in the association of MD with specific BC subtypes.

Conclusions: Our study, the largest to date on this issue, confirms that MD is an independent risk factor for all BC subtypes in either BRCA1 and BRCA2 mutation carriers, and should be considered a phenotype risk marker in this context.

No MeSH data available.


Related in: MedlinePlus