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Background. Women with proliferative breast disease (PD) have been observed to have an increased risk of breast cancer. The authors evaluated the effect of PD on breast cancer risk in a case–control study among participants of the Breast Cancer Detection Demonstration Project (BCDDP). Methods. More than 280,000 women were screened in the BCDDP at 29 centers. Study subjects were selected from BCDDP participants who underwent biopsy that revealed benign breast tissue. There were five BCDDP centers for which histologic slides were available on more than 85% of the benign biopsy specimens. Case patients for this study were the 95 women from these five centers who had breast cancer develop during follow‐up. Two matched control patients who did not have breast cancer develop were selected for each case. The biopsy slides were reviewed by two pathologists who were blinded with regard to cancer outcome. Results. Women with atypical hyperplasia (AH) had 4.3 times the breast cancer risk of women without PD (95% confidence interval [CI], 1.7–11). In women with PD lacking AH, the relative risk was 1.3 (95% CI, 0.77–2.2). A family history of breast cancer (FH) increased breast cancer risk 2.4 times (95% CI, 1.4–4.3). The joint occurrence of FH and AH had a strong synergistic effect on breast cancer risk. Conclusions. AH is a reliable marker of increased breast cancer risk among women undergoing breast biopsy.

Rationale: Asymptomatic relatives of patients with familial interstitial pneumonia (FIP), the inherited form of idiopathic interstitial pneumonia, carry increased risk for developing interstitial lung disease.Objectives: Studying these at-risk individuals provides a unique opportunity to investigate early stages of FIP pathogenesis and develop predictive models of disease onset.Methods: Seventy-five asymptomatic first-degree relatives of FIP patients (mean age, 50.8 yr) underwent blood sampling and highresolution chest computed tomography (HRCT) scanning in an ongoing cohort study; 72 consented to bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies. Twenty-seven healthy individuals were used as control subjects.Measurements and Main Results: Eleven of 75 at-risk subjects (14%) had evidence of interstitial changes by HRCT, whereas 35.2% had abnormalities on transbronchial biopsies. No differences were noted in inflammatory cells in BAL between at-risk individuals and control subjects. At-risk subjects had increased herpesvirus DNA in cell-free BAL and evidence of herpesvirus antigen expression in alveolar epithelial cells (AECs), which correlated with expression of endoplasmic reticulum stress markers in AECs. Peripheral blood mononuclear cell and AEC telomere length were shorter in at-risk individuals than healthy control subjects. The minor allele frequency of the Muc5B rs35705950 promoter polymorphism was increased in at-risk subjects. Levels of several plasma biomarkers differed between at-risk subjects and control subjects, and correlated with abnormal HRCT scans.Conclusions: Evidence of lung parenchymal remodeling and epithelial dysfunction was identified in asymptomatic individuals at risk for FIP. Together, these findings offer new insights into the early pathogenesis of idiopathic interstitial pneumonia and provide an ongoing opportunity to characterize presymptomatic abnormalities that predict progression to clinical disease.

A man with usual interstitial pneumonia (age of onset 58 years) was previously found to have an Ile73Thr (I73T) surfactant protein C (SFTPC) mutation. Genomic DNA from the individual and two daughters (aged 39 and 43 years) was sequenced for the I73T mutation and variations in ATP-binding cassette A3 (ABCA3). All three had the I73T SFTPC mutation. The father and one daughter (aged 39 years) also had a transversion encoding an Asp123Asn (D123N) substitution in ABCA3. The daughters were evaluated by pulmonary function testing and high-resolution CT (HRCT). Neither daughter had evidence of disease, except for focal subpleural septal thickening on HRCT scan in one daughter (aged 39 years). This daughter underwent bronchoscopy with transbronchial biopsies revealing interstitial fibrotic remodeling. These findings demonstrate that subclinical fibrotic changes may be present in family members of patients with SFTPC mutation-associated interstitial lung disease and suggest that ABCA3 variants could affect disease pathogenesis.

This report describes the results of transvaginal color Doppler sonography (TV-CDS) of 43 surgically proved ovarian masses. Waveform analyses of the signals arising from specific vessels (i.e., peripheral, central, septal) adjacent to and within these masses were correlated to those seen on macroscopic pathologic evaluation. The mean and standard deviation of the pulsatility indices (PI) of 32 benign lesions (1.8 +/- 0.8) were higher than 11 malignant ones (0.8 +/- 0.6) (P = 0.03). However, the range of benign (4.0 to 0.7) and malignant (1.5 to 0.4) lesions did overlap. Low PIs (less than 1.0) were found in five relatively benign lesions (one case each of dermoid cyst, cystadenoma containing a dermoid cyst, endometrioma, benign sclerosing stromal tumor, and thecoma), but also in all 11 malignant or borderline malignant lesions (nine cystadenocarcinomas, two germ cell tumors), causing an overlap between the PIs of some benign and malignant masses. With a 100% negative predictive value, our preliminary data suggest that TV-CDS can effectively exclude malignancy. However, with a positive predictive value of 73%, one in four malignant lesions diagnosed by TV-CDS will be benign.