Predictors of Contralateral Breast Cancer in BRCA Negative Women

Breast cancer is the most common cancer diagnosis and second leading cause of death in women. Risk factors associated with breast cancer include: increased age, alcohol consumption, cigarette smoking, white race, physical inactivity, benign breast conditions, reproductive and hormonal factors, dietary factors, and family history. Hereditary breast and ovarian cancer syndrome (HBOC) is caused by mutations in the BRCA1 and BRCA2 genes. Women carrying a mutation in these genes are at an increased risk to develop a second breast cancer. Contralateral breast cancer is the most common second primary cancer in patients treated for a first breast cancer. Other risk factors for developing contralateral breast cancer include a strong family history of breast cancer, age of onset of first primary breast cancer, and if the first primary was a lobular carcinoma, which has an increased risk of being bilateral. A retrospective chart review was performed on a select cohort of women in an IRB approved database at MD Anderson Cancer Center. The final cohort contained 572 women who tested negative for a BRCA1 or BRCA2 mutation, had their primary invasive breast cancer diagnosed under the age of 50, and had a BRCAPro risk assessment number over 10%. Of the 572 women, 97 women developed contralateral breast cancer. A number of predictors of contralateral breast cancer were looked at between the two groups. Using univariable Cox Proportional Hazard model, thirteen statistically interesting risk factors were found, defined as having a p-value under 0.2. Multivariable stepwise Cox Proportional Hazard model found four statistically significant variables out of the thirteen found in the univariable analysis. In our study population, the incidence of contralateral breast cancer was 17%. Four statistically significant variables were identified. Undergoing a prophylactic mastectomy was found to reduce the risk of developing contralateral breast cancer, while not having a prophylactic mastecomy, a young age at primary diagnosis, having a positive estrogen receptor status of the primary tumor, and having a family history of breast cancer increased a woman’s risk to develop contralateral breast cancer.

(Table 1) K-Ar age of alkaline igneous rocks from the Jan Mayen fracture zone

Bottom morphology of the Jan Mayen transform fracture zone and rock chemistry data show that petrological and chemical specific features of igneous rocks can result from higher permeability of the transform fracture zone and deeper penetration of ocean water into the lithosphere in comparison with rift zones of the Kolbeinsey and Mohn's mid-ocean ridges. Age of alkaline magmatism of the Jan Mayen fracture zone is similar to that of rift zones due to palingenesis of metamorphosed and hydrated mantle and crustal rocks.

Distribution, genesis and age of the Schlagwasser breccia (Warstein anticline, Rhenish massif)

The name "Schlagwasser breccia" is a synopsis of several debris flows in the Warstein area, which can be derived from the Warstein carbonate platform and the Scharfenberg reef. Though only locally developed, the breccia is important for the understanding of paleogeography and sedimentology in the Eastern Sauerland. Considering this breccia some gravitational-resedimentary slide movements between a high, consisting of reef carbonates, and a basin with flinz beds can be pointed out. From the uppermost Middle Devonian to the lowermost Lower Carboniferous several slides yielded the sedimentary components building up the 30 to 50 m thick polymict breccia. Some breccias were redeposited repeatedly as can be verified by different conodont maxima in single samples. Supplying area was the western part of the Warstein high, from which the slide masses glided off to the East and Southeast, more seldom to the West and Westsouthwest. All conodont zones from the upper Middle Devonian up to the lowermost Carboniferous could be identified in the Schlagwasser breccia. Therefore, an uninterrupted continuous sedimentation must have been prevalent in the supplying area; today this area nearly is denuded of flinz beds and cephalopod limestones. The slide masses spread transgressively to the East up to a substratum consisting of different units as massive limestone, flinz beds and cephalopod limestone; they are overlapped by Hangenberg beds, alum schists and siliceous rocks of the Lower Carboniferous. Parts of the substratum were transported during the progress of the slide masses. Proximal and distal parts of the flow masses can be distinguished by the diameter of the pebbles. Graded bedding and banking structures are marked only rarely. Way of transport was up to 3 km. Differently aged slide masses do not always overlap, but are placed side by side, too. Usually the slide masses do not spread out upon a greater area during sedimentation, but form closely limited debris flows. Synsedimentary fracturing and tilting of the reef platform, epirogenetic movements and seaquakes caused the slides. The entire formation period of the breccia includes about 20 millions of years. The longevity of the events points to solid paleomorphological situations around the eastern margin of the carbonate platform.