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Stuart J Schnitt

Publications and source records attributed to Stuart J Schnitt.

At least 19 recordsLinked to original sources
PubMed2007

Magnitude and laterality of breast cancer risk according to histologic type of atypical hyperplasia: results from the Nurses' Health Study.

BACKGROUND: Atypical hyperplasia (AH) in a benign breast biopsy is associated with an increased breast cancer risk. However, the influence of the histologic type of AH on the magnitude and laterality of breast cancer risk is poorly defined. METHODS: The authors conducted a case-control study of benign breast disease and breast cancer risk nested within the Nurses' Health Study (395 cases, 1610 controls). Benign breast biopsy slides were reviewed and categorized as showing nonproliferative lesions, proliferative lesions without atypia, or AH. Slides that showed AH were categorized further as atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH). RESULTS: The odds ratio (OR) for breast cancer among all women with AH was 4.1 (95% confidence interval [95% CI], 2.9-5.8). However, among premenopausal women, breast cancer risk was higher for women with ALH (OR, 7.3; 95% CI, 3.8-14.2) than for women with ADH (OR, 3.1; 95% CI, 2.0-4.8). Overall, 58.9% of invasive breast cancers that developed in women with AH were in the ipsilateral breast, and the frequency of ipsilateral breast cancer was similar for women with ALH (61.3%) and women with ADH (55.9%; P = .66). CONCLUSIONS: Women with AH in a benign breast biopsy were at a substantially increased risk for the development of breast cancer. Among premenopausal women, the risk appeared to be greater for those with ALH than those with ADH. Because only approximately 60% of cancers that develop in women with AH occur in the ipsilateral breast, for the purposes of clinical management, these lesions are viewed best as markers of a generalized (bilateral) increase in breast cancer risk.

Adolescent↗
PubMed2006

The influence of family history on breast cancer risk in women with biopsy-confirmed benign breast disease: results from the Nurses' Health Study.

BACKGROUND: An association between histologic category of benign breast disease (BBD) and breast cancer risk has been well documented. However, the influence of a positive family history (FH) on breast cancer risk among women with biopsy-confirmed BBD is less certain. METHODS: The authors conducted a nested case-control study of BBD and breast cancer risk among 2005 women who were enrolled in the Nurses' Health Study. Cases were women with breast cancer who had a previous benign breast biopsy (n = 395 women). Controls were women who also had previous biopsy-confirmed BBD but were free from breast cancer at the time the corresponding case was diagnosed (n = 1610 women). BBD slides were reviewed and categorized as either nonproliferative lesions, proliferative lesions without atypia, or atypical hyperplasia (AH). RESULTS: Compared with women who had nonproliferative lesions and no FH, women who had proliferative lesions without atypia and a positive FH had a higher breast cancer risk (odds ratio [OR], 2.45; 95% confidence interval [95% CI], 1.61-3.70) than women with no FH (OR, 1.51; 95% CI, 1.12-2.06; P = .07). Among women who had AH, the OR for the development of breast cancer was 4.38 (95% CI, 2.93-6.55) for those with no FH and 5.37 (95% CI, 3.01-9.58) for those with a positive FH (P = .57). There was no significant interaction between the type of BBD and FH (P = .74). CONCLUSIONS: A positive FH of breast cancer slightly increased the breast cancer risk among women who had proliferative lesions without atypia. The increase in risk of breast cancer associated with FH was not significant among women who had AH.

Adult↗
PubMed2006

A prospective study of conservative surgery without radiation therapy in select patients with Stage I breast cancer.

PURPOSE: The effectiveness of radiation therapy (RT) in reducing local recurrence after breast-conserving surgery (BCS) in unselected patients with early stage invasive breast cancer has been demonstrated in multiple randomized trials. Whether a subset of women can achieve local control without RT is unknown. In 1986, we initiated a prospective one-arm trial of BCS alone for highly selected breast-cancer patients. This report updates those results. METHODS AND MATERIALS: Eighty-seven (of 90 planned) patients enrolled from 1986 until closure in 1992, when a predefined stopping boundary was crossed. Patients were required to have a unicentric, T1, pathologic node-negative invasive ductal, mucinous, or tubular carcinoma without an extensive intraductal component or lymphatic-vessel invasion. Surgery included local excision with margins of at least 1 cm or a negative re-excision. No RT or systemic therapy was given. RESULTS: Results are available on 81 patients (median follow-up, 86 months). Nineteen patients (23%) had local recurrence (LR) as a first site of failure (average annual LR: 3.5 per 100 patient-years of follow-up). Other sites of first failure included 1 ipsilateral axilla, 2 contralateral breast cancers, and 4 distant metastases. Six patients developed other (nonbreast) malignancies. Nine patients have died, 4 of metastatic breast cancer and 5 of unrelated causes. CONCLUSIONS: Even in this highly selected cohort, a substantial risk of local recurrence occurred after BCS alone with margins of 1.0 cm or more. These results suggest that with the possible exception of elderly women with comorbid conditions, radiation therapy after BCS remains standard treatment.

Adenocarcinoma, Mucinous↗
PubMed2006

Prospective study of wide excision alone for ductal carcinoma in situ of the breast.

PURPOSE: It has been hypothesized that wide excision alone with margins > or = 1 cm may be adequate treatment for small, grade 1 or 2 ductal carcinoma in situ (DCIS). To test this hypothesis, we conducted a prospective, single-arm trial. METHODS: Entry criteria included DCIS of predominant grade 1 or 2 with a mammographic extent of < or = 2.5 cm treated with wide excision with final margins of > or = 1 cm or a re-excision without residual DCIS. Tamoxifen was not permitted. The accrual goal was 200 patients. RESULTS: In July 2002, the study closed to accrual at 158 patients because the number of local recurrences met the predetermined stopping rules. The median age was 51 and the median follow-up time was 40 months. Thirteen patients developed local recurrence as the first site of treatment failure 7 to 63 months after study entry. The rate of ipsilateral local recurrence as first site of treatment failure was 2.4% per patient-year, corresponding to a 5-year rate of 12%. Nine patients (69%) experienced recurrence of DCIS and four (31%) experienced recurrence with invasive disease. Twelve recurrences were detected mammographically and one was palpable. Ten were in the same quadrant as the initial DCIS and three were elsewhere within the ipsilateral breast. No patient had positive axillary nodes at recurrence or subsequent metastatic disease. CONCLUSION: Despite margins of > or = 1 cm, the local recurrence rate is substantial when patients with small, grade 1 or 2 DCIS are treated with wide excision alone. This risk should be considered in assessing the possible use of radiation therapy with or without tamoxifen in these patients.

Aged↗
PubMed2006

Interobserver reproducibility in the diagnosis of flat epithelial atypia of the breast.

Columnar cell lesions (CCLs) of the breast with low-grade/monomorphic-type cytologic atypia are being identified increasingly in biopsies performed owing to mammographic microcalcifications. The WHO Working Group on the Pathology and Genetics of Tumours of the Breast recently introduced the term 'flat epithelial atypia' (FEA) for these lesions. However, the ability of pathologists to reproducibly diagnose FEA and to distinguish it from CCLs without atypia has not been previously evaluated. Eight pathologists with an interest in breast pathology participated in a study to address this issue. The study reference pathologist provided the other seven study pathologists with a Powerpoint tutorial that included written criteria for, and representative images of, FEA and CCLs without atypia (ie, columnar cell change and columnar cell hyperplasia). Following review of the tutorial, the study pathologists examined images in Powerpoint format from 30 CCLs and were instructed to categorize each as either 'FEA' or 'not atypical'. Overall agreement among the eight pathologists was 91.8% (95% CI, 84.0-96.9%), and the multi-rater kappa value was 0.83 (95% CI, 0.67-0.94), which is within the 'excellent agreement' range. Agreement was slightly better for determining absence of FEA (92.8%: 95% CI, 84.1-97.4%), than for determining its presence (90.4%: 95% CI, 79.9-96.7%). We conclude that the diagnosis of FEA and its distinction from CCLs without atypia is highly reproducible with the use of available diagnostic criteria.

Breast↗
PubMed2006

Ductal carcinoma in situ with basal-like phenotype: a possible precursor to invasive basal-like breast cancer.

Basal-like carcinomas have recently been identified in gene expression profiling studies as a subtype of invasive breast cancer. These lesions are estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative (triple negative), and typically express basal cytokeratins, epidermal growth factor receptor (EGFR), and/or c-kit. As poorly differentiated invasive ductal carcinomas, they presumably have a ductal carcinoma in situ (DCIS) precursor with similar cytologic and immunophenotypic features. However, the frequency and even the existence of a DCIS lesion with an immunophenotype analogous to that of invasive basal-like carcinomas have not been previously evaluated. We studied 66 cases of high nuclear grade DCIS using antibodies to ER, PR, HER2, three basal cytokeratins, EGFR, and c-kit to determine the frequency of the triple negative phenotype, and to determine the relationship between the triple negative phenotype and expression of basal cytokeratins and other biomarkers characteristically expressed by invasive basal-like carcinomas. Four cases (6%) exhibited the triple negative phenotype; the remaining cases showed other combinations of ER, PR, and HER2 expression (nontriple negative). Basal cytokeratins, EGFR, or both were expressed by all four triple negative lesions, but by only 21 of 51 (42%) nontriple negative cases (P = 0.04). We conclude that a small proportion of high-grade ductal carcinomas in situ exhibit an ER-negative/PR-negative/HER2-negative (triple negative) phenotype, and these lesions more commonly show expression of basal cytokeratins and/or EGFR than nontriple negative high-grade DCIS. Given that invasive breast cancers typically share immunophenotypic features with the ductal carcinoma in situ from which they arise, our findings raise the possibility that the triple-negative, basal cytokeratin and/or EGFR-positive DCIS lesions we identified represent a precursor lesion to invasive basal-like carcinomas.

Adult↗
PubMed2006

Intracystic papillary carcinomas of the breast: a reevaluation using a panel of myoepithelial cell markers.

Intracystic papillary carcinomas (IPC) of the breast have traditionally been considered to be variants of ductal carcinoma in situ (DCIS). However, it is not clear if all lesions categorized histologically as IPC are truly in situ carcinomas, or if some such lesions might represent circumscribed or encapsulated nodules of invasive papillary carcinoma. Given that the demonstration of a myoepithelial cell (MEC) layer around nests of carcinoma cells is a useful means to distinguish in situ from invasive carcinomas of the breast in problematic cases, assessment of the presence or absence of a MEC layer at the periphery of the nodules that comprise these lesions could help resolve this issue. We studied the presence and distribution of MEC at the periphery of the nodules of 22 IPC and, for comparison, 15 benign intraductal papillomas using immunostaining for 5 highly sensitive markers that recognize various MEC components: smooth muscle myosin heavy chain, calponin, p63, CD10, and cytokeratin 5/6. All 22 lesions categorized as IPC showed complete absence of MEC at the periphery of the nodules with all 5 markers. In contrast, a MEC layer was detected around foci of conventional DCIS present adjacent to the nodules of IPC. Furthermore, all benign intraductal papillomas, including those of sizes comparable to those of IPC, showed a MEC layer around virtually the entire periphery of the lesion with all 5 MEC markers. In conclusion we could not detect a MEC layer at the periphery of the nodules of any of 22 lesions categorized histologically as IPC. One possible explanation for this observation is that these are in situ lesions in which the delimiting MEC layer has become markedly attenuated or altered with regard to expression of these antigens, perhaps due to their compression by the expansile growth of these lesions within a cystically dilated duct. Alternatively, it may be that at least some lesions that have been categorized as IPC using conventional histologic criteria actually represent circumscribed, encapsulated nodules of invasive papillary carcinoma. Regardless of whether these lesions are in situ or invasive carcinomas, available outcome data indicate that they seem to have an excellent prognosis with adequate local therapy alone. Therefore, we believe it is most prudent to continue to manage patients with these lesions as they are currently managed (ie, similar to patients with DCIS) and to avoid categorization of such lesions as frankly invasive papillary carcinomas. Given our observations, we favor the term "encapsulated papillary carcinoma" over "intracystic papillary carcinoma" for circumscribed nodules of papillary carcinoma surrounded by a fibrous capsule in which a peripheral layer of MEC is not identifiable.

Aged↗
PubMed2006

Diagnostic architectural and dynamic features at breast MR imaging: multicenter study.

PURPOSE: To prospectively determine the prevalence and predictive value of three-dimensional (3D) and dynamic breast magnetic resonance (MR) imaging and contrast material kinetic features alone and as part of predictive diagnostic models. MATERIALS AND METHODS: The study protocol was approved by the institutional review board or ethics committees of all participating institutions, and informed consent was obtained from all participants. Although study data collection was performed before HIPAA went into effect, standards that would be compliant with HIPAA were adhered to. Data from the International Breast MR Consortium trial 6883 were used in the analysis. Women underwent 3D (minimum spatial resolution, 0.7 x 1.4 x 3 mm; minimal temporal resolution, 4 minutes) and dynamic two-dimensional (temporal resolution, 15 seconds) MR imaging examinations. Readers rated enhancement shape, enhancement distribution, border architecture, enhancement intensity, presence of rim enhancement or internal septations, and the shape of the contrast material kinetic curve. Regression was performed for each feature individually and after adjustment for associated mammographic findings. Multivariate models were also constructed from multiple architectural and dynamic features. Areas under the receiver operating characteristic curve (Az values) were estimated for all models. RESULTS: There were 995 lesions in 854 women (mean age, 53 years +/- 12 [standard deviation]; range, 18-80 years) for whom pathology data were available. The absence of enhancement was associated with an 88% negative predictive value for cancer. Qualitative characterization of the dynamic enhancement pattern was associated with an Az value of 0.66 across all lesion architectures. Focal mass margins (Az = 0.76) and signal intensity (Az = 0.70) were highly predictive imaging features. Multivariate models were constructed with an Az value of 0.880. CONCLUSION: Architectural and dynamic features are important in breast MR imaging interpretation. Multivariate models involving feature assessment have a diagnostic accuracy superior to that of qualitative characterization of the dynamic enhancement pattern.

Adolescent↗
PubMed2006

Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342.

INTRODUCTION: The response to paclitaxel varies widely in metastatic breast cancer. We analyzed data from CALGB 9342, which tested three doses of paclitaxel in women with advanced disease, to determine whether response and outcomes differed according to HER2, hormone receptor, and p53 status. METHODS: Among 474 women randomly assigned to paclitaxel at a dose of 175, 210, or 250 mg/m2, adequate primary tumor tissue was available from 175. Immunohistochemistry with two antibodies and fluorescence in situ hybridization were performed to evaluate HER2 status; p53 status was determined by immunohistochemistry and sequencing. Hormone receptor status was obtained from pathology reports. RESULTS: Objective response rate was not associated with HER2 or p53 status. There was a trend toward a shorter median time to treatment failure among women with HER2-positive tumors (2.3 versus 4.2 months; P = 0.067). HER2 status was not related to overall survival (OS). Hormone receptor expression was not associated with differences in response but was associated with longer OS (P = 0.003). In contrast, women with p53 over-expression had significantly shorter OS than those without p53 over-expression (11.5 versus 14.4 months; P = 0.002). In addition, triple negative tumors were more frequent in African-American than in Caucasian patients, and were associated with a significant reduction in OS (8.7 versus 12.9 months; P = 0.008). CONCLUSION: None of the biomarkers was predictive of treatment response in women with metastatic breast cancer; however, survival differed according to hormone receptor and p53 status. Triple negative tumors were more frequent in African-American patients and were associated with a shorter survival.

Black or African American↗
PubMed2005

Added cancer yield of MRI in screening the contralateral breast of women recently diagnosed with breast cancer: results from the International Breast Magnetic Resonance Consortium (IBMC) trial.

OBJECTIVE: To estimate the added cancer yield of magnetic resonance imaging (MRI) over mammography in the contralateral breast of patients with a recent diagnosis of breast cancer. METHODS: We conducted a prospective, international study of mammography and MRI in women with a recent diagnosis of unilateral breast cancer. Each subject received a mammogram, clinical breast exam (CBE), and MRI of the unaffected breast within a 90 day time period. Definitive diagnosis of suspicious findings was determined through biopsy and central pathology review. RESULTS: Of the 103 eligible women included in study analyses, MRI detected 4 cancers in the contralateral breast while mammography detected none. MRI resulted in 12% (95% CI, 6%-20%) of women recommended for biopsy and 10% of women undergoing additional biopsy. The added cancer yield of MRI was 4% (95% CI, 1%-10%) and the positive predictive value of an abnormal MRI was 33% (95% CI, 10%-65%). Forty percent (4/10) of the biopsies performed based on the MRI recommendation were positive for malignancy. CONCLUSION: In women with a recent breast cancer diagnosis, approximately 4% will have an otherwise occult invasive breast cancer detected in the opposite breast by MRI alone.

Biopsy↗
PubMed2005

MRI detection of distinct incidental cancer in women with primary breast cancer studied in IBMC 6883.

BACKGROUND: Prior single institution studies suggest MRI may improve the assessment of the extent of cancer within the breast, and thus reduce the risk of leaving macroscopic disease in the breast following breast conservation therapy. We report on the rate of MRI and mammography detection of foci of distinct incidental cancer in a prospective, multi center trial involving 426 women with confirmed breast cancer at 15 institutions in the US, Canada, and Germany. METHODS: Women underwent mammography and MRI prior to biopsy of the suspicious index lesion. Additional incidental lesions (IL) greater than 2 cm from the index lesion that were detected by mammography and MRI were noted and characterized. Biopsy recommendations were associated with ILs given an assessment of suspicious or highly suspicous (BiRads 4 and 5). These assessments were considered a positive test. RESULTS: MRI had a significantly higher yield of confirmed cancer ILs than mammography (0.18 (95%CI: 0.142-0.214) for MRI versus 0.072 (95%CI: 0.050-0.100) for mammography). The cancer ILs detected by MRI alone appeared to be similar to those detected by mammography with respect to size and histology. The percentage of biopsies of ILs that resulted in a cancer diagnosis was similar between the modalities (MRI 0.72(95%CI: 0.6-0.81); Mammography 0.85 (95%CI: 0.62-0.96)). CONCLUSIONS: These results suggest that consideration needs to be given regarding the integration of breast MRI into the pretreatment evaluation of women seeking breast conservation therapy.

Biopsy↗
PubMed2005

Benign breast disease, recent alcohol consumption, and risk of breast cancer: a nested case-control study.

INTRODUCTION: Alcohol consumption is a well-established risk factor for breast cancer. Some studies have suggested that the risk of breast cancer associated with alcohol consumption is greater for women with a history of benign breast disease (BBD). We hypothesized that among women with biopsy-confirmed BBD, recent alcohol consumption would increase the risk of breast cancer in women with proliferative breast disease to a greater extent than in women with nonproliferative breast disease. METHODS: We conducted a nested case-control study in the Nurses' Health Study I and II. The cases (n = 282) were women diagnosed with incident breast cancer, with a prior biopsy-confirmed breast disease. The controls (n = 1,223) were participants with a previous BBD biopsy, but without a diagnosis of breast cancer. Pathologists reviewed benign breast biopsy slides in a blinded fashion and classified the BBD as nonproliferative, proliferative without atypia, or atypical hyperplasia, according to standard criteria. RESULTS: Women with nonproliferative breast disease consuming > or = 15 g of alcohol per day had a nonsignificant 67% increased risk of breast cancer (odds ratio = 1.67; 95% confidence interval 0.65 to 4.34) compared with nondrinkers. There was no evidence that recent alcohol consumption increased the risk of breast cancer to a greater extent in women with proliferative BBD than among women with nonproliferative BBD (P for interactio n = 0.20). CONCLUSION: Contrary to our a priori hypothesis, there was no evidence that recent alcohol consumption increased the risk of breast cancer to a greater extent among women with proliferative BBD than among women with nonproliferative BBD.

Adult↗
PubMed2005

Screening women at high risk for breast cancer with mammography and magnetic resonance imaging.

BACKGROUND: The authors compared the performance of screening mammography versus magnetic resonance imaging (MRI) in women at genetically high risk for breast cancer. METHODS: The authors conducted an international prospective study of screening mammography and MRI in asymptomatic, genetically high-risk women age >/= 25 years. Women with a history of breast cancer were eligible for a contralateral screening if they had been diagnosed within 5 years or a bilateral screening if they had been diagnosed > 5 years previously. All examinations (MRI, mammography, and clinical breast examination [CBE]) were performed within 90 days of each other. RESULTS: In total, 390 eligible women were enrolled by 13 sites, and 367 women completed all study examinations. Imaging evaluations recommended 38 biopsies, and 27 biopsies were performed, resulting in 4 cancers diagnosed for an overall 1.1% cancer yield (95% confidence interval [95%CI], 0.3-2.8%). MRI detected all four cancers, whereas mammography detected one cancer. The diagnostic yield of mammography was 0.3% (95%CI, 0.01-1.5%). The yield of cancer by MRI alone was 0.8% (95%CI, - 0.3-2.0%). The biopsy recommendation rates for MRI and mammography were 8.5% (95%CI, 5.8-11.8%) and 2.2% (95%CI, 0.1-4.3%). CONCLUSIONS: Screening MRI in high-risk women was capable of detecting mammographically and clinically occult breast cancer. Screening MRI resulted in 22 of 367 of women (6%) who had negative mammogram and negative CBE examinations undergoing biopsy, resulting in 3 additional cancers detected. MRI also resulted in 19 (5%) false-positive outcomes, which resulted in benign biopsies.

Adult↗
PubMed2005

Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy: results from the Nurses' Health Study.

BACKGROUND: Studies of patients with ductal carcinoma in situ (DCIS) "treated" by diagnostic biopsy alone have been rare, but provide important opportunities to gain insights into the natural history of these lesions. METHODS: During a review of 1877 breast biopsy specimens in a nested case-control study of benign breast disease and breast carcinoma risk, the authors identified 13 biopsy specimens with DCIS that were originally diagnosed as benign. Because each of these women was initially given a benign diagnosis, they received no treatment beyond the diagnostic biopsy. RESULTS: When compared with women with nonproliferative lesions, the odds ratio (OR) for the development of invasive breast carcinoma among those with retrospectively identified DCIS (n = 6) was 13.5 (95% confidence interval [CI], 3.7-49.7). The OR for the development of any subsequent invasive or in situ breast carcinoma event (n = 10) was 20.1 (95% CI, 6.1-66. 5). A retrospective review of these DCIS biopsy specimens revealed that the nuclear grade was low in four lesions, intermediate in six, and high in three. None showed comedo-type necrosis. Invasive carcinomas developed among women with DCIS of all nuclear grades. All 10 breast carcinoma events (100%) were in the ipsilateral breast. CONCLUSIONS: These results provided further evidence that patients with DCIS who received no treatment beyond a diagnostic biopsy were at substantially increased risk for developing ipsilateral invasive breast carcinoma, and that the increased risk in this setting was seen in DCIS of low, intermediate, and high nuclear grades.

Adult↗
PubMed2005

Ultrahigh-resolution and 3-dimensional optical coherence tomography ex vivo imaging of the large and small intestines.

BACKGROUND: Ultrahigh-resolution optical coherence tomography (OCT) has an axial resolution of <5 microm, 2 to 3 times finer than standard OCT. This study investigates ultrahigh-resolution and three-dimensional OCT for ex vivo imaging of the large and small intestines and correlates images with histology. METHODS: Ultrahigh-resolution OCT imaging was performed on fresh surgical specimens from the large and small intestines in the pathology laboratory, and images were correlated with histology. OCT was performed at 1.3-microm wavelength with 4.5-microm axial x 11-microm transverse resolution and at 1.1-microm wavelength with 3.5-microm axial x 6-microm transverse resolution. Three-dimensional OCT also was investigated. RESULTS: Normal and pathologic areas from 23 surgical specimens of the large and small intestines were imaged. Ultrahigh-resolution OCT distinguished the epithelial layer of the mucosa and visualized individual villi, glands, and crypts. Finer transverse resolutions improved visualization of features, e.g., the epithelium, but reduced the depth of field. Architectural distortion of glands from inflammatory and neoplastic processes was observed. Three-dimensional rendering enabled visualization of surface pit pattern and mucosal folds as well as subsurface crypt microstructure. CONCLUSIONS: This study evaluates new OCT technology and can provide a baseline for interpreting future ultrahigh-resolution endoscopic OCT studies.

Adult↗
PubMed2005

HER2 protein overexpression in estrogen receptor-positive ductal carcinoma in situ of the breast: frequency and implications for tamoxifen therapy.

Recent clinical data have suggested that the efficacy of tamoxifen in reducing the risk of local recurrence following lumpectomy and radiation therapy in patients with ductal carcinoma in situ (DCIS) is limited to patients with estrogen receptor (ER)-positive lesions. However, it is currently not known if HER2 protein overexpression might be associated with reduced tamoxifen benefit in patients with ER-positive DCIS, as has been suggested in patients with ER-positive invasive breast cancer and in preclinical models. Moreover, the frequency of HER2 overexpression in ER-positive ductal carcinoma in situ has not been previously evaluated in detail. To address this issue, we studied ER expression and HER2 overexpression in 148 cases of DCIS using a sensitive double immunostaining technique and assessed the frequency of ER expression and HER2 overexpression in relation to each other and in relation to DCIS grade. Overall, ER expression was seen in 114 cases (77%) and HER2 protein overexpression was seen in 42 cases (28%). Of 114 ER-positive ductal carcinoma in situ, 14 (12%) showed concurrent HER2 protein overexpression, and all 14 of these DCIS lesions were of high nuclear grade. In addition, in all 14 ER-positive DCIS cases that showed HER2 overexpression, double immunostaining demonstrated that ER and HER2 protein were coexpressed by the same neoplastic cells. We conclude that a subset of ER-positive DCIS show concomitant overexpression of HER2 protein. Whether or not HER2 overexpression is associated with a diminished response to tamoxifen in patients with ER-positive DCIS will require investigation in clinical outcome studies.

Antineoplastic Agents, Hormonal↗
PubMed2005

Early life factors and incidence of proliferative benign breast disease.

Proliferative benign breast disease is a marker of increased breast cancer risk, yet little is known about its etiology. Most studies of benign breast disease have focused only on risk factors in adulthood, despite growing evidence that factors in early life influence breast cancer risk. We explored the relations of several early life factors with incidence of proliferative benign breast disease among 71,896 premenopausal women in the Nurses' Health Study II who recalled their body fatness at young ages, physical activity in adolescence, birthweight, and history of being breastfed. Between 1991 and 1997, 901 of these women were identified as having proliferative benign breast disease from a centralized pathology review. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazards models. Greater childhood body fatness (ages 5-10) was associated with decreased risk of proliferative benign breast disease; the multivariate RR (95% CI) for the most overweight compared with the most lean was 0.61 (0.44-0.86; P(trend) < 0.0001) and remained significant after adjustment for current body mass index. Body mass index at age 18 was also inversely associated with incidence of proliferative benign breast disease, with a multivariate RR (95% CI) of 0.67 (0.52-0.88) for those who were > or =25 kg/m(2) compared with those who were <19 kg/m(2) (P(trend) = 0.001). There were no clear associations for physical activity in adolescence, birthweight, or being breastfed. These results indicate that premenopausal women who were heavier at young ages have lower incidence of proliferative benign breast disease, consistent with previous findings for breast cancer.

Adiposity↗