Regina Kroiss

Magnetic resonance imaging of the breast improves detection of invasive cancer, preinvasive cancer, and premalignant lesions during surveillance of women at high risk for breast cancer.

Purpose: To assess the diagnostic accuracy of mammography, ultrasound, and magnetic resonance imaging (MRI) of the breast in the surveillance of women at high risk for breast cancer. Experimental Design: In this prospective comparison study, women at high risk for breast cancer were offered annual surveillance examinations, consisting of mammography, ultrasound, and MRI, at a single tertiary care breast center. The sensitivity and specificity of each modality was based on the histopathologic evaluation of suspicious findings from all modalities plus the detected interval cancers. Results: Three hundred and twenty-seven women underwent 672 complete imaging rounds. Of a total of 28 detected cancers, 14 were detected by mammography, 12 by ultrasound, and 24 by MRI, which resulted in sensitivities of 50%, 42.9%, and 85.7%, respectively (P < 0.01). MRI detected not only significantly more invasive but also significantly more preinvasive cancers (ductal carcinoma in situ). Mammography, ultrasound, and MRI led to 25, 26, and 101 false-positive findings, which resulted in specificities of 98%, 98%, and 92%, respectively (P < 0.05). Thirty-five (35%) of these false-positive findings were atypical ductal hyperplasias, lesions considered to be of premalignant character. Nine (26%) of those were detected by mammography, 2 (6%) with ultrasound, and 32 (91%) with MRI (P < 0.01). Conclusion: Our results show that MRI of the breast improves the detection of invasive cancers, preinvasive cancers, and premalignant lesions in a high-risk population and should therefore become an integral part of breast cancer surveillance in these patients.

The validity of complex breast cysts after surgery.

BACKGROUND Breast cysts are the most common cause of benign breast masses. Simple breast cysts do not need further evaluation, but complex breast cysts require additional assessment due to the potential presence of malignancy. However, these complex cysts have rarely been examined and quantified according to the associated cancer detection rate. Our study is the first investigation to evaluate the malignancy rate of complex breast cysts identified by histopathological results. METHODS Imaging findings of complex cysts were correlated retrospectively with clinical and pathologic outcomes. We detected a malignancy rate of 14%. Sonographic criteria of a complex cyst such as thick cyst wall (P = .0006), lobulation (P = .01), and hyperechogenicity (P = .04) were predictive of neoplasm. Two or more criteria combined were associated with a 13.6-fold higher risk of malignancy (P <.0001). CONCLUSION Based on our results we reinforce the importance of adequate assessment of complex breast cysts to prevent a missed or delayed diagnosis of malignancy.

Central European BRCA2 mutation carriers: birth cohort status correlates with onset of breast cancer.

BACKGROUND Mutations in brca1 and 2 genes lead to a significant increase in the lifetime risk of developing breast (BC) and ovarian cancer (OC). There are indications that birth cohort can influence the cancer risk in brca1 mutation carriers. Therefore, we investigated the risks for BC and OC associated with brca2 mutations in a cohort of female mutation carriers of a genetically heterogeneous Central European population. PATIENTS AND METHODS This study included 246 women in whom a functional mutation in the brca2 gene had been identified at our institution. At the time of analysis, 153 women had developed cancer (142 BC, 9 OC, 2 BC and OC). Risks were estimated using the product limit method. The log rank test was used to compare different strata. RESULTS After correction for risk-reducing surgeries, the cumulative risk of developing cancer to age 70 was found to be 88% for BC (95% CI 81-95%) and 31% for OC (95% CI 17-45%). Female brca2 mutation carriers born in 1958 or later were at a significantly higher risk of developing BC at a younger age (p<0.001), while no such age cohort-dependent correlation was found for OC. CONCLUSION The age cohort-dependent early onset in BC in women born after 1958 strongly suggests the importance of exogenous factors such as lifestyle modification while this does not seem to be the case for OC. Female brca2 mutation carriers should be counseled about their age cohort-dependent breast cancer risk.

Impact of lifestyle factors on preneoplastic changes in prophylactic oophorectomies of BRCA mutation carriers

BRCA mutation carriers are at high risk of developing ovarian cancer. Ovarian malignancies are usually identified at an advanced stage with poor prognosis, attributed to inadequate options of early detection. Because of its risk-reducing effect of nearly 96%, prophylactic salpingo-oophorectomy is still the leading option for risk-reduction in women with a positive BRCA mutation status. The presence of ovarian cancer precursor lesions, such as epithelial inclusion cysts (EICs) or cortical invaginations (CIs), has previously been discussed in several studies with diverse conclusions. We retrospectively investigated a large and consistent population (n=94) of BRCA mutation carriers for the presence of potential preneoplastic and neoplastic changes. We also examined the role of specific lifestyle factors. Ninety-four women with disease-associated germline BRCA1 or BRCA2 mutations were included in this retrospective study. All women had undergone genetic counseling and prophylactic salpingo-oophorectomy, which was performed at a mean age of 43.33 years (range 27–66). Histological slides of both ovaries were reviewed by an independent pathologist. Data concerning lifestyle factors were collected from medical files and questionnaires. Two malignant lesions (2.1%), one bilateral serous papillary adenocarcinoma of the epithelial surface and one adenocarcinoma of the peritoneum with involvement of the left adnexa, and one lesion (1.1%) with obvious malignant potential, one mucinous borderline tumor of the right ovary, have been identified. We registered a high prevalence of CIs (30; 31.9%) and EICs (44; 46.8%) in prophylactically removed ovaries of BRCA mutation carriers. A significant correlation (P=0.002) was found with regard to the presence of EICs in women with increased BMI. Concerning the regular consumption of alcohol as a risk factor for premalignant lesions, in particular CIs, a statistically insignificant trend (P=0.083) was noted. Overweight women seem to be at risk of developing more cortical invaginations than women of normal weight. To improve the final outcome of the disease, women at increased risk of ovarian cancer should be appropriately informed of potential increased risk factors.

Hereditary Breast and Ovarian Cancer: Structures of Care in Austria

Mutations in the BRCA1 or BRCA2 genes result in a significantly increased risk of breast and ovarian cancer. Austrian women who carry a BRCA1 mutation have a risk of 85% for breast cancer and 53% for ovarian cancer up to 70 years of age. At-risk women have 2 medical options: closely monitored early detection using mammography, breast ultrasound, and MRI, as well as tumor markers and vaginal ultrasound, or real risk reduction through prophylactic removal of the breast tissue and/or the ovaries. As awareness of such a high risk of disease may cause a great deal of distress, and because prophylactic surgeries offer only very drastic measures for risk reduction, a special multidisciplinary care concept is of particular importance. This care starts with comprehensive genetic counseling before performing molecular genetic analysis and must be continued after a genetic predisposition for breast and ovarian cancer has been identified. Right from the start, special schooling in Austria has ensured that patients in all cooperating genetic counseling centers are counseled, selected, and followed- up according to the same criteria.