Biomedical subjects

Mark E Sherman

Publications and source records attributed to Mark E Sherman.

At least 19 recordsLinked to original sources

PubMed2026

Menopausal timing and senescent-immune coupling in age-related lobular involution of the human breast: a longitudinal cohort study.

BACKGROUND: Incomplete postmenopausal breast involution leaves persistent epithelial-rich lobules and elevated breast density in about 40% of women and is associated with higher breast cancer risk, but why remodelling stalls remains unclear. METHODS: We studied a longitudinal cohort of 81 women with paired benign breast biopsies (baseline age 45-55 years; follow-up 2-10 years), all with baseline NanoString transcriptomics and two-timepoint digital morphometry, and with multiplex immunofluorescence in spatial-imaging subsets (baseline n = 14-16 depending on panel; follow-up n = 14). A separate postmenopausal endpoint cohort (12 women: eight noninvoluted, four completely involuted), profiled by genome-wide expression array and multiplex immunofluorescence, defined the persistent-lobule phenotype. FINDINGS: Noninvoluted postmenopausal tissue retained a proliferation-competent, tumour-associated epithelial state and showed immune accumulation at lobular boundaries with reduced access to p16+ (senescence-associated) epithelial foci. The same SASP and innate immune programmes that predicted slower involution across the menopausal transition predicted faster involution after menopause. Follow-up boundary CD45→p16 engagement was directionally consistent with this reversal in Pre→Post and Post→Post women. Spatial imaging resolved this reversal into a perimenopausal stall architecture and a postmenopausal clearance-associated architecture marked by direct CD16+ innate-effector engagement of p16+ epithelium; macrophage targeting provided convergent support (two-sided exact permutation interaction p = 0.0077). INTERPRETATION: Menopausal timing conditions whether senescent-immune programmes couple to productive clearance or to spatially uncoupled surveillance and persistent risk-associated tissue. Biomarker interpretation should therefore be anchored to menopausal timing. FUNDING: Casey DeSantis Cancer Fund and US National Cancer Institute.

Humans↗

PubMed2007

The Bethesda Interobserver Reproducibility Study (BIRST): a web-based assessment of the Bethesda 2001 System for classifying cervical cytology.

BACKGROUND: The Bethesda System (TBS) along with its companion atlas was updated in 2001 to improve standardization, clarity, and reproducibility of cervical cytology reporting. METHODS: The authors used a novel web-based format to compare assessments of 77 images demonstrating a range of classical and borderline cytologic changes by a self-selected group of United States cytotechnologists (n = 216) and pathologists (n = 185). RESULTS: Participants were highly experienced, with 71.2% of cytotechnologists and 53.0% of pathologists reporting >10 years of practice. The mean percentage of exact agreement with the panel was slightly though significantly higher for cytotechnologists (57.0%) compared with pathologists (53.4%), adjusted for experience (P = .004); cervical cytology percentage effort (P = .0005); or cervical accession volume (P = .0002). Compared with the TBS panel, exact agreement was achieved for 55.1% of image ratings compared with 82.3% agreement at the level of Negative vs non-Negative for images with a single-panel interpretation. Agreement with the panel was highest for images classified as Low-Grade Squamous Intraepithelial Lesion and lowest for Atypical Squamous Cells qualified as either of Undetermined Significance or Cannot Exclude a High-Grade Squamous Intraepithelial Lesion. Reviewers were less sensitive in identifying high-grade glandular lesions than they were in identifying high-grade squamous lesions at any threshold (P < .001). CONCLUSIONS: Morphologic appearances of images were more important determinants than participants' academic or professional degrees with regard to interobserver reproducibility in classifying cervical cytology images. Experienced cytotechnologists and pathologists performed similarly. Participants achieved higher sensitivity for identifying high-grade squamous lesions than they did for high-grade glandular lesions. These findings demonstrated that web-based studies may be useful in assessing interobserver agreement in classifying images.

Adenocarcinoma↗

PubMed2007

Estimating age-specific breast cancer risks: a descriptive tool to identify age interactions.

OBJECTIVE: Clarifying age-specific female breast cancer risks and interactions may provide important etiologic clues. METHOD: Using a population-based case-control study in Poland (2000-2003) of 2,386 incident breast cancer cases and 2,502 control subjects aged 25-74 years, we estimated age-specific breast cancer incidence rates according to risk factors. RESULTS: Breast cancer risks were elevated among women with positive family history (FH), younger age at menarche, older age at first full-term birth, nulliparity, exogenous hormonal usage, and reduced physical activity (PA). Notwithstanding overall risks, we observed statistically significant quantitative (non-crossover) and qualitative (crossover) age interactions for all risk factors except for FH and PA. For example, nulliparity compared to parity reduced breast cancer risk among women ages 25-39 years then rates crossed or reversed, after which nulliparity increased relative risks among women ages 40-74 years. CONCLUSION: Though quantitative age interactions could be expected, qualitative interactions were somewhat counterintuitive. If confirmed in other populations, qualitative interactions for a continuous covariate such as age will be difficult to reconcile in a sequential (multistep or monolithic) 'stochastic' breast cancer model. Alternatively, the reversal of relative risks among younger and older women suggests subgroup heterogeneity with different etiologic mechanisms for early-onset and late-onset breast cancer types.

Adult↗

PubMed2006

"Sip volume" as a quality indicator in liquid-based cervical cytology.

BACKGROUND: Introduction of nonmicroscopic cervical screening techniques creates the potential for liquid-based cytology specimens to be sent for human papillomavirus (HPV) testing, automated screening, or other assays prior to microscopic quality assessment. It was hypothesized that the volumes required to prepare ThinPreps ("sip volumes") represent indicators of specimen quality. METHODS: A stratified random sample of 505 enrollment ThinPreps were assessed in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS) to evaluate associations between sip volume and slide cellularity, cellular distribution, and clinical outcomes. Masked assessments included counting cells and qualitative evaluations. RESULTS: Sip volumes were highest among women aged 18-19 or > or =35 years (P = .01), higher during the secretory menstrual phase (P < .0001), and lower among women with a history of Chlamydia infection (P = .04). Low cellularity was associated with Atypical squamous cells-cannot exclude high-grade squamous intra-epithelial lesion (ASC-H) interpretations at the clinical centers (P = .04). Sip volumes were related to cellularity (P < .0001) and cellular distribution (P < .0001). Sip volumes < or =2.0 mL were associated with lower cellularity and both low and high sip volumes yielded less homogeneous cell deposition. However, sip volume was unrelated to the overall performance of cytology and HPV testing. CONCLUSIONS: Extremely low sip volumes are associated with hypocellular ThinPreps, and very low and high sip volumes more often show uneven cellular distribution. Although results of cytology and HPV testing in ALTS were generally unrelated to sip volume, results with other protocols or assays may vary, suggesting that microscopic assessment of specimens with extreme sip volumes prior to nonmicroscopic testing may be useful.

Adolescent↗

PubMed2006

Serum concentrations of estrogens, sex hormone-binding globulin, and androgens and risk of breast cancer in postmenopausal women.

We assessed the relationship between serum concentrations of estrogens, androgens, and sex hormone-binding globulin and risk of breast cancer among postmenopausal women. Study participants provided serum prior to breast biopsy or mastectomy in 3 hospitals in Grand Rapids, Michigan between 1977 and 1987. A total of 179 subjects with localized breast cancer were compared to 152 subjects with nonproliferative breast changes that have not been associated with elevated breast cancer risk. Increasing serum concentrations of estrone and estrone sulfate were associated with increases in breast cancer risk; the odds ratios (ORs) in the fourth quartiles compared to the first were 2.3 (95% confidence interval (CI) 1.1-4.6) for both (p-trend = 0.02 and 0.03, respectively). Estradiol and bioavailable estradiol concentrations were associated with nonstatistically significant increases in risk. Androstenediol levels were associated with risk (p-trend = 0.01); the OR in the fourth compared to the first quartile was 2.2 (95% CI 1.0-4.6). Testosterone, dehydroepiandrosterone and androstenedione levels were not associated with increased risk. Sex hormone-binding globulin was associated with a nonsignificant decrease in risk. Associations with estrone and estrone sulfate persisted after adjustment for androstenediol (ORs for fourth compared to first quartiles were 2.0 (95% CI 0.9-4.5) and 2.2 (95% CI 1.0-4.6), respectively (p-trend = 0.16 for both). The association with androstenediol was attenuated after adjustment for estrone (OR for fourth compared to first quartile was 1.6 (95% CI 0.7-3.6); p-trend = 0.13). Higher serum concentrations of estrogens were associated with increased breast cancer risk in postmenopausal women. Androgen levels were not independently associated with substantially increased risk.

Aged↗

PubMed2006

Intrauterine environment and breast cancer risk in a population-based case-control study in Poland.

High estrogen exposure in utero may increase breast cancer risk later in life. However, studies of the associations between perinatal factors presumed to affect the fetal hormonal environment and breast cancer risk are inconsistent. We used data from a population-based case-control study of 2,386 incident breast cancers and 2,502 controls in Poland to evaluate risks associated with various perinatal characteristics. After adjusting for confounders, we found a significant trend (p = 0.01) of breast cancer risk with birth weight (OR = 1.54, 95% CI 1.08-2.19 for birth weights >4,000 g vs. <2,500 g). Subjects with a high birth order (> or =6) were at reduced risk (OR = 0.81, 0.61-1.06) when compared with first born subjects. Birth weight was somewhat a stronger risk predictor among subjects whose cancers were diagnosed at 50 years of age or older (OR = 1.84, 1.19-2.85) than among those with cancers diagnosed at younger ages (OR = 1.14, 0.61-2.12). Subjects whose mothers smoked during their pregnancies were at slightly higher risk than those who never smoked (OR = 1.21, 0.99-1.47), but the risk was similar to mothers who only smoked at other times (OR = 1.22, 0.81-1.84). Breast cancer risk was not related to paternal smoking, maternal age, gestational age or twin status. Our results add support to the growing evidence that some perinatal exposures may relate to breast cancer risk. Additional studies are needed to confirm associations and clarify the biologic mechanisms underlying these associations.

Adult↗

PubMed2006

Cervical cytology of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H): characteristics and histologic outcomes.

BACKGROUND: The 2001 Bethesda System category of atypical squamous cells (ASC) denotes changes suggestive, but inconclusive for, a squamous intraepithelial lesion (SIL). ASC is subcategorized as: 1) "undetermined significance (ASC-US)," when changes suggest low-grade or indeterminate-grade SIL and 2) "cannot exclude high-grade squamous intraepithelial lesion (ASC-H)," when a cancer precursor is suspected. METHODS: To better define the characteristics of ASC-H, the authors analyzed and compared human papillomavirus (HPV) testing data and outcomes after 2 years for participants in the Atypical Squamous Cells of Undetermined Significance Low-Grade SIL Triage Study (ALTS), a randomized trial of 5060 women. RESULTS: Among women with thin-layer cytology findings of ASC-H, 84% tested positive for HPV, 50% (95% confidence interval [95% CI], 41%-60%) were diagnosed with cervical intraepithelial neoplasia (CIN) type 2+, and 30% (95% CI, 22-39%) were diagnosed with CIN3+. Positive HPV tests and diagnoses of CIN2+ and CIN3+ were found to be more common among women with ASCH compared with those with ASC-US, but the highest frequencies were found to be associated with high-grade SIL. For women age < 35 years with ASC-H, HPV detection exceeded 85%, whereas only 4 of 10 women (40%) age >/=35 years tested positive for HPV (P = 0.009). CONCLUSIONS: A finding of ASC-H seems to confer a substantially higher risk for CIN2+ and CIN3+ than ASC-US. Immediate colposcopy may be the appropriate management for young women with ASC-H, but the utility of HPV testing for managing older women with ASC-H requires additional study.

Colposcopy↗

PubMed2006

Tobacco smoking, NAT2 acetylation genotype and breast cancer risk.

The role of active and passive cigarette smoking in breast cancer etiology remains controversial. Using data from a large population-based case-control study in Poland (2386 cases, 2502 controls) conducted during 2000-2003, we examined the associations between active and passive smoking overall and for different age categories. We also evaluated differences in risk by estrogen receptor (ER) and progesterone receptor (PR) status in tumors, and the potential modification of the smoking association by N-acetyl transferase 2 (NAT2) genotype. Women ever exposed to passive smoking at home or at work had a risk of breast cancer similar to those never exposed to active or passive smoking (OR (95%CI) = 1.11 (0.85-1.46), and no trends were observed with increasing hours/day-years of passive smoking exposure. Active smoking was associated with a significant increase in risk only among women younger than 45 years of age (OR (95%CI) = 1.95 (1.38-2.76); 1.15 (0.93-1.40); 0.91 (0.77-1.09) for < 45, 45-55 and > 55 years of age, respectively; p-heterogeneity < 0.001 for < 45 vs. > 55 years) and prevailed for both ER+ and ER- tumors. The smoking association among women < 45 years was stronger for current than former smokers, and a significant trend was observed with duration of smoking (p = 0.04). NAT2 slow vs. rapid/intermediate acetylation genotype was not related to breast cancer risk (0.99 (0.87-1.13)), and did not significantly modify the smoking relationships. In conclusion, our data indicate that passive smoking is not associated with breast cancer risk; however, active smoking might be associated with an increased risk for early onset breast cancers.

Acetylation↗

PubMed2006

Relationships of human papillomavirus type, qualitative viral load, and age with cytologic abnormality.

Persistent cervical infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancer. Cytologic abnormalities are the manifestations of HPV infections used to identify women at risk. To compare the potential of the full range of anogenital HPV genotypes to induce cytopathic effects, we examined the influences of HPV type, viral load, and age on cytopathology among 1,222 women having a single HPV type at enrollment into a 10,000-woman population-based study in Costa Rica. Cervical specimens were tested for approximately 40 HPV types by MY09/MY11 L1 primer PCR and type-specific dot blot hybridization. Types were organized by phylogenetic species and cancer risk. PCR signal strength served as a qualitative surrogate for viral load. Overall, 24.8% [95% confidence interval (95% CI), 22.4-27.3] of single prevalent HPV infections had concurrent abnormalities (atypical squamous cells or worse) ranging from 0.0% to 80.0% based on HPV type. Noncarcinogenic alpha3/alpha15 types, although highly prevalent, uncommonly caused cytologic abnormalities (13.1%; 95% CI, 9.8-17.0). In contrast, one quarter to nearly one half of infections with a single major carcinogenic species type (alpha9/alpha11/alpha7/alpha5/alpha6) produced abnormalities. Greater abnormalities were observed with increasing qualitative viral load of carcinogenic types; fewer abnormalities were observed among older women (>54 years). A high percentage (46.2%) of detected abnormalities in women infected with HPV16 or related alpha9 types were high grade or worse, consistent with strong carcinogenicity, compared with 10.7% in women infected with alpha7 types, including HPV18, a major cause of adenocarcinoma. The lack of evident severe abnormalities associated with HPV18 and related HPV types might have implications for screening for poorly detected glandular and alpha7-related lesions.

Adult↗

PubMed2006

Weight, height, and body mass index and risk for ovarian cancer in a cohort study.

PURPOSE: Reported associations between ovarian cancer and body size are inconsistent. We assessed ovarian cancer and anthropometry in the Breast Cancer Detection Demonstration Project Follow-Up Study. METHODS: The 46,026 participants completed a baseline interview and mailed questionnaires between 1979 and 1998. By using multiple sources, we identified 346 incident ovarian cancers during follow-up. We calculated rate ratios (RRs) and 95% confidence intervals (CIs) to estimate relative risks for developing ovarian cancer associated with height and weight (measured 1973 to 1980) and self-reported current and usual adult weight (collected during follow-up). RESULTS: Neither taller height (> or =66 versus <62 inches; RR, 0.90; 95% CI, 0.64-1.26) nor greater weight (> or =161 versus < or =120 lbs; RR, 1.09; 95% CI, 0.77-1.55) was associated with ovarian cancer. Compared with normal weight (body mass index [BMI], 18.5 to 24.9 kg/m(2)), overweight (BMI, 25 to 29.9 kg/m(2); RR, 1.00; 95% CI, 0.78-1.29) and obesity (BMI, 30 to 34.9 kg/m(2); RR, 0.94; 95% CI, 0.59-1.48) were not associated with ovarian cancer. Severe obesity (BMI > or = 35 kg/m(2)) produced a nonsignificantly elevated RR (1.55; 95% CI, 0.84-2.84). Associations with histologic types and statistical interactions with menopausal status and hormone therapy use were null. CONCLUSIONS: Based on height and weight measured before baseline, overweight and obesity were not significantly associated with ovarian cancer in this cohort.

Adult↗

PubMed2006

Pathological characteristics of cervical adenocarcinoma in a multi-center US-based study.

OBJECTIVE: Difficulties in detecting cervical adenocarcinoma early are well known. We report a detailed pathology review of cervical adenocarcinoma subtypes, comparing growth patterns and appearance of non-neoplastic epithelium to inform possible clues for disease progression and early detection. METHODS: This analysis includes 154 women aged 18-69 years and diagnosed with incident in situ or invasive adenocarcinoma (AC), adenosquamous (AS), or other rare cervical glandular tumors from 1992-1996 in six U.S. medical centers. A pathology review panel evaluated histological features from original diagnostic slides. RESULTS: Higher tumor grade (P < 0.001) and vascular invasion (P = 0.002) were more common in AS compared to AC. Adenocarcinoma in situ (AIS) was also more common among AC than AS (P = 0.002). Among AC with cervical intraepithelial carcinoma (CIN), AIS and cribriform patterns were more common than AC without CIN (P = 0.01). Further, non-endometrioid AC had higher tumor grade (P = 0.01) and stromal responses (P = 0.02) than endometrioid AC. Finally, although microglandular hyperplasia is historically thought to be related to oral contraceptive (OC) use, our data do not support this notion. CONCLUSION(S): AS appears to be either diagnosed later or histologically more aggressive than AC, and among AC subtypes, there are distinct histologic characteristics. Further research is needed to identify precursor lesions for early detection of AC and particularly for AS where AIS may not be a common precursor.

Adenocarcinoma↗

PubMed2006

Clarifying breast cancer risks associated with menopausal hormone therapy.

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Breast Neoplasms↗

PubMed2006

Genetic variation of Cytochrome P450 1B1 (CYP1B1) and risk of breast cancer among Polish women.

Four single nucleotide polymorphisms (SNPs) in CYP1B1 (Ex2 + 143 C > G, Ex2 + 356 G > T, Ex3 + 251 G > C, Ex3 + 315 A > G) cause amino acid changes (R48G, A119S, L432V and N453S, respectively) and are associated with increased formation of catechol estrogens; however, epidemiologic evidence only weakly supports an association between these variants and breast cancer risk. Because genetic variability conferring increased susceptibility could exist beyond these putative functional variants, we comprehensively examined the common genetic variability within CYP1B1. A total of eight haplotype-tagging (ht)SNPs (including Ex3 + 315 A > G), in addition to two putatively functional SNPs (Ex2 + 143 C > G and Ex3 + 251 G > C), were selected and genotyped in a large case-control study of Polish women (1995 cases and 2296 controls). Haplotypes were estimated using the expectation-maximization algorithm, and overall differences in the haplotype distribution between cases and controls were assessed using a global score test. We also evaluated levels of tumor CYP1B1 protein expression in a subset of 841 cases by immunohistochemistry, and their association with genetic variants. In the Polish population, we observed two linkage disequilibrium (LD)-defined blocks. Neither haplotypes (global P-value of 0.99 and 0.67 for each block of LD, respectively), nor individual SNPs (including three putatively functional SNPs) were associated with breast cancer risk. CYP1B1 was expressed in most tumor tissues (98%), and the level of expression was not related to the studied genetic variants. We found little evidence for modification of the estimated effect of haplotypes or individual SNPs by age, family history of breast cancer, or tumor hormone receptor status. The present study provides strong evidence against the existence of a substantial overall association between common genetic variation in CYP1B1 and breast cancer risk.

Adult↗

PubMed2006

Construction and validation of tissue microarrays of ductal carcinoma in situ and terminal duct lobular units associated with invasive breast carcinoma.

Construction of tissue microarrays (TMAs) to efficiently characterize large sets of noninvasive epithelial lesions in the breast by immunohistochemistry is an appealing investigative approach, but presents technical challenges. We report methodologic studies performed to optimize methods for building TMAs from noninvasive breast tissues collected in a large case-control study of breast cancer. Using a manual arraying technique with 2.0-mm diameter needles, we constructed TMAs from specimens obtained from 32 women with breast cancer containing the following targets: (1) 28 terminal duct lobular units (TDLUs); (2) 28 ductal carcinomas in situ, and (3) 23 invasive carcinomas. Using careful target selection, we achieved representation of approximately 80% of noninvasive targets with sustained preservation through section 30 of the TMAs. Immunohistochemical staining of TDLU targets demonstrated positive staining for estrogen receptor (ER) in 30.8% of tubules and for progesterone receptor (PR) in 50.0%. To establish an efficient method to evaluate staining results in TDLUs, we created a categorical scoring system to approximate the percentage of tubules containing positive stained cells (<10%, 10% to 50%, >or=50%), and compared the results with those obtained by tubule counting. Comparison between the two methods demonstrated exact agreement for 70.8% of ER and 79.2% of PR stains without two-category discrepancies. ER/PR expression levels in multiple (up to 4) noninvasive targets of the same tissue type (TDLU or DCIS) from a single block showed good correlation. These data suggest that it is feasible to produce TMAs of noninvasive breast structures, albeit with careful selection of targets, and that immunostains of such cores may permit efficient immunohistochemical characterization of peritumoral tissues. Additional exploration of this approach is needed.

Breast Neoplasms↗

PubMed2006

Cervical tissue collection methods for RNA preservation: comparison of snap-frozen, ethanol-fixed, and RNAlater-fixation.

Promising molecular techniques may allow for testing of novel and complex hypotheses such as defining gene expression profiles in specific cells, tumors, or their microenvironments. For most large cancer epidemiologic and population-based studies, however, application of such promising techniques may not be possible owing to constraints of specimen preservation from paraffin-embedded tissues. Alternative methods would ideally preserve tissue morphology and not degrade DNA or RNA. We conducted a comparison of snap-freezing (freezing with liquid nitrogen), ethanol-fixation with low melt polyester wax embedding, and RNAlater-preservation techniques to determine which method was optimal for subsequent assessment of gene expression changes in cervical cancer. From each of 15 women with cancer and 30 without, we procured 3 pieces of cervical tissue and compared snap-freezing, ethanol-fixation, and RNAlater-preservation techniques. Despite slight loss in morphologic quality from snap-frozen cervix tissues, RNA quality was equivalent to or better than RNAlater-preserved tissues and significantly exceeded that from ethanol-fixed/polyester wax embedded tissue. In conclusion, despite the moderate logistical constraints in set-up that required either liquid nitrogen or dry ice on-site for snap-freezing tissue, the ease of downstream processing and consistent high quality RNA made it preferable to the other 2 methods.

Cervix Uteri↗

PubMed2006

Ovarian volume: determinants and associations with cancer among postmenopausal women.

Clinical studies have reported associations between ovarian stromal hyperplasia and the diagnosis of hormonally related tumors such as endometrial cancer. To assess the hypothesis that characteristics of benign ovaries among postmenopausal women are related to risk for breast, endometrial, and colon cancer, we analyzed systematically collected transvaginal ultrasound data for participants enrolled in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Among women without cancer, median ovarian volume declined with age from 1.25 cm3 for women between ages 55 and 59 years to 1.0 cm3 for those between ages 65 and 69 years. African American and Caucasian women had larger median ovarian volumes than Asians. Larger ovarian volume was also associated with the highest quartiles of height and weight and ever having smoked. After adjusting for race, age, parity, body mass, smoking, and hormone use, women with median ovarian volumes >or=3.0 cm3 were at increased risk for breast cancer [odds ratio (OR), 1.42; 95% confidence interval (95% CI), 1.11-1.70], endometrial cancer (OR, 1.97; 95% CI, 1.12-3.48), and colon cancer (OR, 2.00; 95% CI, 1.25-3.21). Significant trends of risk with increasing volume were found only for breast and endometrial cancers. We conclude that large ovaries among postmenopausal women may represent a marker of risk for hormonally related tumors. Confirmation of these findings in future studies, including analyses of serum hormone levels and tissues, may provide insights into hormonal carcinogenesis among older women.

Aged↗

PubMed2006

Comparison of age distribution patterns for different histopathologic types of breast carcinoma.

BACKGROUND: Historically, female breast carcinoma has been viewed as an etiologically homogeneous disease associated with rapidly increasing incidence rates until age 50 years, followed by a slower rate of increase among older women. More recent studies, however, have shown distinct age incidence patterns for female breast cancer when stratified by estrogen receptor (ER) expression and/or histopathologic subtypes, suggesting etiologic heterogeneity. MATERIALS AND METHODS: To determine if different age incidence patterns reflect etiologic heterogeneity (more than one breast cancer type within the general breast carcinoma), we applied "smoothed" age histograms at diagnosis (density plots) and a two-component statistical mixture model to all breast carcinoma cases (n = 270,124) in the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. These overall patterns were then reevaluated according to histopathologic type, race, and ER expression. RESULTS: A bimodal age distribution at diagnosis provided a better fit to the data than a single density for all breast carcinoma populations, except for medullary carcinoma. Medullary carcinomas showed a single age distribution at diagnosis irrespective of race and/or ER expression. CONCLUSIONS: Distinct age-specific incidence patterns reflected bimodal breast cancer populations for breast carcinoma overall as well as for histopathologic subtypes, race, and ER expression. The one exception was medullary carcinoma. Of note, medullary carcinomas are rare tumors, which are associated with germ-line mutations in the BRCA1 gene. These descriptive and model-based results support emerging molecular data, suggesting two main types of breast carcinoma in the overall breast cancer population.

Adenocarcinoma↗

PubMed2005

Impact of hysterectomy on endometrial carcinoma rates in the United States.

In the United States, endometrial carcinoma incidence rates, uncorrected for hysterectomy prevalence, are higher among white women than black women. We estimated corrected endometrial carcinoma rates by racial/ethnic groups and age (30-74 years) for 1992-2000 using data from the Surveillance, Epidemiology, and End Results program and the Behavioral Risk Factor Surveillance Survey. Hysterectomy prevalence was higher among black women than among Hispanic and white non-Hispanic women. Correcting for hysterectomy prevalence increased age-adjusted endometrial carcinoma rates per 10(5) woman-years from 29.2 to 48.7 (66.8% increase) overall, from 14.6 to 28.5 (95.3% increase) in blacks, from 18.8 to 29.6 (57.6% increase) in Hispanics, and from 33.2 to 54.9 (65.1%) in white non-Hispanics. This correction reduced the rate ratio for white non-Hispanics compared with blacks from 2.27 to 1.93. Among blacks but not Hispanics or white non-Hispanics, the endometrial carcinoma risk factors of obesity and diabetes were more prevalent among hysterectomized than nonhysterectomized women. Failure to correct for hysterectomy prevalence may lead to underestimates of endometrial carcinoma risk, especially among blacks. The high prevalence of hysterectomy among blacks with strong endometrial cancer risk factors may partly account for lower cancer rates in this group.

Adult↗