PubMed Health⌕ Search

Biomedical subjects

Kevin S Hughes

Publications and source records attributed to Kevin S Hughes.

18 recordsLinked to original sources
PubMed2006

Breast cancer diagnosis in women < or = 40 versus 50 to 60 years: increasing size and stage disparity compared with older women over time.

BACKGROUND: Women < or = 40 years account for 5% of new breast cancer diagnoses. Although there is increased awareness of genetic and other breast cancer risk factors, it is not clear whether this has resulted in earlier diagnosis in young women. METHODS: A database review identified 8892 women treated for breast cancer from 1980 to 2002. We compared 925 women aged < or = 40 years with 2362 women aged 50 to 60 years. The mean and median tumor size and lymph node status were determined for each group. RESULTS: There were significant differences in tumor size and lymph node status in younger versus older women. From 1980 to the mid 1990s, tumor size and nodal status did not differ. Since the mid 1990s, tumor size has decreased more rapidly for women aged 50 to 60 years than for those < or = 40 years. In 1998 to 2002, the mean tumor size reached a plateau of 1.8 cm in women 50 to 60 years, compared with a plateau of 2.4 cm in women < or = 40 years (P < .001). The median tumor size in 1998 to 2002 was 1.4 cm in women 50 to 60 years compared with 1.9 cm in women < or = 40 years (P < .001). Lymph node status was also significantly different during 1998 to 2002: 23.9% positive in women 50 to 60 years versus 35.2% in women < or = 40 years (P < .001). CONCLUSIONS: Since the 1980s, women aged 50 to 60 years have enjoyed a greater decrease in tumor size and percentage with positive nodes. These data could be the result of ineffective screening of younger women or of more aggressive tumor biology. Further study is required to determine whether more effective identification and screening of young, high-risk women can result in earlier detection.

Adult↗
PubMed2006

Long-term risk of false-positive screening results and subsequent biopsy as a function of mammography use.

PURPOSE: To retrospectively determine the long-term risk of false-positive mammographic assessments and to evaluate the effect of screening regularity on the risk of false-positive events. MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was waived. Retrospective analysis was performed for the occurrence of false-positive assessments among 83,511 women who underwent 314,185 mammographic examinations from January 1, 1985, to February 19, 2002. Data were collected from a database that had been assembled prospectively. Two categories of false-positive events were examined: biopsies that did not reveal cancer and false-positive mammographic assessments. Rates of false-positive events were compared by using a chi2 analysis, and 95% confidence limits were calculated. Because comparisons of multiple pairs were considered, all P values that demonstrated statistical significance exceeded the requirement of the Bonferroni correction. RESULTS: While the overall rates of biopsies that did not reveal cancer and of false-positive mammographic assessments were similar to those found in other studies, most of the burden of false-positive events was borne by women who underwent intermittent screening. Long-term rates of false-positive events were lower among women who underwent regular screening than among those who underwent intermittent screening. In the 5-year group, 2.9% of women who underwent five mammographic examinations over the next 5 years had biopsy results that did not reveal cancer, whereas 4.6% of women who underwent three mammographic examinations over the next 5 years had biopsy results that did not reveal cancer. For women who underwent regular screening, the risk of undergoing biopsies that did not reveal cancer declined over time to 0.25% per year after several years of screening, a value that is lower than the risk of these events among women who did not undergo screening. The rate of false-positive mammographic assessments was also lower for women who underwent regular screening than for those who underwent intermittent screening. CONCLUSION: Prompt annual attendance for mammographic screening reduces the occurrence of false-positive mammographic results.

Adult↗
PubMed2005

Prevalence of hereditary breast/ovarian carcinoma risk in patients with a personal history of breast or ovarian carcinoma in a mammography population.

BACKGROUND: Identifying BRCA1 and BRCA2 mutation carriers is increasingly important as new management options show promise in decreasing morbidity and mortality in these women. The authors sought to determine the prevalence of family histories suggestive of a hereditary breast carcinoma syndrome in a cohort of patients with a personal history of breast and/or ovarian carcinoma presenting for mammography. METHODS: The authors reviewed the family histories of all women with a history of breast or ovarian carcinoma presenting for mammography over a 37-week period. Using the Myriad model, the authors evaluated the prevalence of family histories with a > or = 10% risk of a BRCA1 or BRCA2 mutation. RESULTS: During the period of the current study, 14,597 women completed a family history questionnaire. Of these women, 1764 had a personal history of breast or ovarian carcinoma, 86.6% had unilateral breast carcinoma, 4.6% had bilateral breast carcinoma, 8.2% had ovarian carcinoma, and 0.5% had both breast and ovarian carcinoma. Overall, 20.6% met the criteria for a > or = 10% risk of mutation according to the Myriad model. This incidence was higher among Ashkenazi women (47.3%) and among patients with a personal history of ovarian carcinoma (35.9%). CONCLUSIONS: Application of the Myriad model to women with a personal history of breast and ovarian carcinoma suggested that approximately 1 in 5 of these women (20.6%) will have family histories suspicious for a genetic mutation. This risk was higher for Ashkenazi women and for those with a personal history of ovarian carcinoma. This prevalence was considerably higher than the rate reported among women with no personal history of cancer, and has significant implications for their management, as well as for the capacity for risk assessment and testing.

Breast Neoplasms↗
PubMed2005

A comparison of sentinel node biopsy before and after neoadjuvant chemotherapy: timing is important.

BACKGROUND: Because neoadjuvant chemotherapy is being used more frequently, the optimal timing of sentinel node biopsy (SNB) remains controversial. We previously evaluated the predictive value of SNB before neoadjuvant chemotherapy in clinically node-negative breast cancer. Our identification rate of the sentinel node among 52 patients before chemotherapy with a mean tumor size of 4 cm was 100%. In this study, we compared the identification rates of SNB before and after neoadjuvant chemotherapy and evaluated the false-negative rate of SNB after chemotherapy. METHODS: A retrospective institutional database review identified 36 women who underwent SNB after neoadjuvant chemotherapy for breast cancer from 1999 to 2004. The initial clinical tumor size and lymph node status, SNB pathology, axillary lymph node dissection pathology, and residual pathologic tumor size were reviewed. RESULTS: Sixteen of 36 patients had a clinically negative axilla before neoadjuvant therapy. SNB after neoadjuvant therapy was successful in 29 patients (80.6%), although 7 patients did not map (19.4%). Six of the 7 patients who failed to map had a clinically positive axilla initially. Axillary disease was found in 6 of 7 of these patients at dissection (85.7%). Of the 29 patients who mapped successfully, 13 (45%) were SNB negative, and 16 (55%) were SNB positive. Of the 13 SNB-negative patients, 2 had a positive axillary lymph node dissection, yielding a false-negative rate of 11%. Thirteen patients who mapped had a clinically positive axilla before therapy (45%). Of the 11 patients with true-negative SNBs, 7 (64%) were clinically node negative at presentation. The initial tumor sizes on examination ranged from 2 to 9 cm (mean, 5.0 cm), and residual pathologic tumor sizes ranged from 0 to 6 cm (mean, 1.8 cm). Failure to map correlated with a clinically positive axilla at presentation (100% vs 45%) but did not correlate with initial tumor size. CONCLUSIONS: Sentinel node identification rates are significantly better when mapping is performed before neoadjuvant chemotherapy (100% vs 80.6%), with failure to map correlated with clinically positive nodal disease at presentation and residual disease at axillary lymph node dissection. Among patients who map successfully after chemotherapy, the false-negative rate is high (11%). Given these findings, we currently recommend SNB before neoadjuvant chemotherapy for clinically node-negative patients, and raise concerns about the use of SNB after neoadjuvant therapy in patients with an initially clinically positive axilla.

Antineoplastic Agents↗
PubMed2005

Breast cancer treatment in older women.

This article presents the author's current approaches to the management of breast cancer in older women, with emphasis on clinical and surgical treatment of the disease in this population. There are controversies surrounding the management of breast cancer in this population regarding adjuvant therapy, radiation therapy and surgical options. We endeavor to address these issues in the article.

Age Factors↗
PubMed2005

Palpable right breast mass in a pregnant woman.

BACKGROUND: A 29-year-old female presented with a palpable right breast mass at a 12-week prenatal visit. She had no family history of breast or ovarian cancer. Ultrasound revealed a 3 cm lobulated mass, which was confirmed to be malignant by a core biopsy. Postmastectomy pathology at 15 weeks' gestation demonstrated this mass to be a stage T2N0M0 high-grade invasive ductal carcinoma with 0/20 axillary nodes involved. A staging CT scan postpartum showed an enlarged right internal mammary lymph node, confirmed by MRI as suspicious for malignancy. INVESTIGATIONS: Physical examination, breast ultrasound, core biopsy, mastectomy, CT scan, MRI. DIAGNOSIS: Pregnancy-associated breast carcinoma. MANAGEMENT: Mastectomy, chemotherapy and radiotherapy.

Adult↗
PubMed2005

Evaluation of hereditary risk in a mammography population.

PURPOSE: BRCA1 and BRCA2 mutations significantly increase a women's lifetime risk of breast and ovarian cancer. Because several management options have shown promise in decreasing morbidity and mortality for these women, identifying potential mutation carriers is increasingly important. We have developed a large-scale method to collect family histories in a population of unaffected women presenting for mammography. We then applied current risk-assessment models to determine the prevalence of women at risk for hereditary breast and ovarian cancer. MATERIALS AND METHODS: We performed a retrospective review of family histories using data collected on all unaffected women presenting for mammography over a 14-week period. The Claus, Myriad II, and Hartmann models for hereditary risk assessment were applied to the survey results. RESULTS: The questionnaire was completed by 5736 women, 695 of whom were excluded because of a personal history of breast or ovarian cancer. Family histories of the remaining 5041 women were evaluated. Totals of 5.9%, 5.2%, and 3.3% of patients, respectively, met criteria for increased risk according to the Hartmann, Myriad II, and Claus models, corresponding to 3.5, 3.1, and 1.9 patients per day. Although 9.2% of patients met criteria for >/=1 model, only 1.4% met criteria for all 3. CONCLUSIONS: Application of available models to a screening population classifies a larger than expected number of women at high risk for a BRCA1 or BRCA2 mutation. New approaches to risk assessment and counseling are needed to apply our knowledge of hereditary risk to a broad population in a practical manner.

Adult↗
PubMed2004

Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer.

BACKGROUND: In women 70 years of age or older who have early breast cancer, it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy. METHODS: Between July 1994 and February 1999, we randomly assigned 636 women who were 70 years of age or older and who had clinical stage I (T1N0M0 according to the tumor-node-metastasis classification), estrogen-receptor-positive breast carcinoma treated by lumpectomy to receive tamoxifen plus radiation therapy (317 women) or tamoxifen alone (319 women). Primary end points were the time to local or regional recurrence, the frequency of mastectomy for recurrence, breast-cancer-specific survival, the time to distant metastasis, and overall survival. RESULTS: The only significant difference between the two groups was in the rate of local or regional recurrence at five years (1 percent in the group given tamoxifen plus irradiation and 4 percent in the group given tamoxifen alone, P<0.001). There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence, distant metastases, or five-year rates of overall survival (87 percent in the group given tamoxifen plus irradiation and 86 percent in the tamoxifen group, P=0.94). Assessment by physicians and patients of cosmetic results and adverse events uniformly rated tamoxifen plus irradiation inferior to tamoxifen alone. CONCLUSIONS: Lumpectomy plus adjuvant therapy with tamoxifen alone is a realistic choice for the treatment of women 70 years of age or older who have early, estrogen-receptor-positive breast cancer.

Aged↗
PubMed2004

Mammographic screening: patterns of use and estimated impact on breast carcinoma survival.

BACKGROUND: Although many studies support the life-saving potential of screening mammography, the actual utilization of screening and the impact of the actual pattern of screening use on the breast carcinoma death rate, remain incompletely understood. In the current report, the authors describe patterns of screening use among women who were examined at a large screening and diagnostic service and estimate the added mortality associated with missed screening mammograms. METHODS: Mammography use was assessed in a population of 72,417 women who received a total of 254,818 screening mammograms at the Massachusetts General Hospital (MGH) Avon Comprehensive Breast Center (Boston, MA) between January 1, 1985, and February 19, 2002. A computer simulation of breast carcinoma growth, spread, and detection of breast carcinoma was used to estimate the likely health consequences of various types of screening use. RESULTS: Both prompt return for annual screening and full use of screening over extended periods of time were rare, and comparison of the MGH population with other populations revealed that the low level of use observed in the MGH population was not atypical. Only 6% of women who received a mammogram in 1992 received all annual mammograms that were available over the next 10 years; the mean number of mammograms received during this period was 5.06, or 51% of the number recommended by the American Cancer Society. Computer simulation results indicate that this underutilization of screening should result in higher mortality levels. Women from traditionally underserved socioeconomic, racial, and ethnic groups, women without insurance, and women who did not speak English had lower levels of use compared with other women. Lower levels of use also were observed among women receiving their first mammogram or who in the past had not returned promptly. Women ages 55-65 years had higher levels of use than did younger or older women. Women who previously had breast carcinoma also had higher levels of screening use. Nonetheless, none of the subpopulations of women stratified by age, race, ethnicity, zip code, income,language, insurance, status, previous screening use, or medical history exhibited a widespread propensity to promptly return for annual screening over an extended period of time. CONCLUSIONS: By many measures, the current analysis is one of the most detailed descriptions of screening use to date. The authors observed a level of screening use that was disappointingly low, with potentially negative health-related consequences, among women across categories defined by racial, ethnic, socioeconomic, and geographic characteristics; insurance status; language; age; medical history; and previous screening use. Improvements in the promptness with which women return to screening appear to have the potential to lead to considerable reductions in breast carcinoma death.

Adult↗
PubMed2003

Racial differences in mammographic breast density.

BACKGROUND: African American women have a lower incidence but a higher mortality from breast carcinoma than Caucasians. A proposed explanation for this discrepancy is the decreased efficacy of screening among African American women. Increased breast density in African American women may result in decreased sensitivity of mammography. The purpose of this article is to determine whether there is a difference in mammographic breast density between African American and Caucasian women. METHODS: A series of 769 women were recruited from 5 sites. Mammograms were reviewed centrally by seven reviewers using Breast Imaging Reporting and Data System categories converted to numeric values. The mean mammographic densities for Caucasian, African American, and Latina patients were compared using a two-way analysis of covariance. The mean values for each race were estimated adjusting for the reader as well as for each patient's age and body mass index (BMI). RESULTS: African American women had the lowest mean breast density. The reported density in this group was 2.43, compared with 2.69 among Caucasians and 2.65 among Latina patients. After adjusting for age and BMI as well as the reader, there was still an independent racial effect on breast density (P = 0.0050). CONCLUSIONS: Mammographic breast density was lower in African American women than in Caucasians and Latinas. This discrepancy may be an intrinsic racial difference due to undetermined causes. Factors, such as the growth rate of tumors and the incidence of calcifications, must be studied to confirm that other forces do not have a negative impact on the efficacy of screening mammograms in African American women.

Adult↗
PubMed2002

Pretest prediction of BRCA1 or BRCA2 mutation by risk counselors and the computer model BRCAPRO.

BACKGROUND: Because BRCA gene mutation testing is costly, occasionally uninformative, and frequently associated with ethical and legal issues, careful patient selection is required prior to testing. Estimation of BRCA gene mutation probability is an important component of pretest counseling, but the accuracy of these estimates is currently unknown. We measured the performance of eight cancer risk counselors and of a computer model, BRCAPRO, at identifying families likely to carry a BRCA gene mutation. METHODS: Eight cancer risk counselors and the computer model BRCAPRO estimated BRCA gene mutation probabilities for 148 pedigrees selected from an initial sample of 272 pedigrees. The final sample was limited to pedigrees with a proband affected by breast or ovarian cancer and BRCA1 and BRCA2 gene sequencing results unequivocally reported as negative or positive for a deleterious mutation. Sensitivity, specificity, negative predictive value, positive predictive value, and areas under receiver operator characteristics (ROC) curves were calculated for each risk counselor and for BRCAPRO. All statistical tests were two sided. RESULTS: Using a greater-than-10% BRCA gene mutation probability threshold, the median sensitivity for identifying mutation carriers was 94% (range = 81% to 98%) for the eight risk counselors and 92% (range = 91% to 92%) for BRCAPRO. Median specificity at this threshold was 16% (range = 6% to 34%) for the risk counselors and 32% (range = 30% to 34%) for BRCAPRO (P =.04). Median area under the ROC curves was 0.671 for the risk counselors (range = 0.620 to 0.717) and 0.712 (range = 0.706 to 0.720) for BRCAPRO (P =.04). There was a slight, but not statistically significant, improvement in all counselor performance measures when BRCAPRO-assigned gene mutation probability information was included with the pedigrees. CONCLUSIONS: Sensitivity for identifying BRCA gene mutation carriers is similar for experienced risk counselors and the computer model BRCAPRO. Because the computer model consistently demonstrated superior specificity, overall discrimination between BRCA gene mutation carriers and BRCA gene mutation noncarriers was slightly better for BRCAPRO.

Breast Neoplasms↗
PubMed2002

BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes.

PURPOSE: To compare genetic test results for deleterious mutations of BRCA1 and BRCA2 with estimated probabilities of carrying such mutations; to assess sensitivity of genetic testing; and to assess the relevance of other susceptibility genes in familial breast and ovarian cancer. PATIENTS AND METHODS: Data analyzed were from six high-risk genetic counseling clinics and concern individuals from families for which at least one member was tested for mutations at BRCA1 and BRCA2. Predictions of genetic predisposition to breast and ovarian cancer for 301 individuals were made using BRCAPRO, a statistical model and software using Mendelian genetics and Bayesian updating. Model predictions were compared with the results of genetic testing. RESULTS: Among the test individuals, 126 were Ashkenazi Jewish, three were male subjects, 243 had breast cancer, 49 had ovarian cancer, 34 were unaffected, and 139 tested positive for BRCA1 mutations and 29 for BRCA2 mutations. BRCAPRO performed well: for the 150 probands with the smallest BRCAPRO carrier probabilities (average, 29.0%), the proportion testing positive was 32.7%; for the 151 probands with the largest carrier probabilities (average, 95.2%), 78.8% tested positive. Genetic testing sensitivity was estimated to be at least 85%, with false-negatives including mutations of susceptibility genes heretofore unknown. CONCLUSION: BRCAPRO is an accurate counseling tool for determining the probability of carrying mutations of BRCA1 and BRCA2. Genetic testing for BRCA1 and BRCA2 is highly sensitive, missing an estimated 15% of mutations. In the populations studied, breast cancer susceptibility genes other than BRCA1 and BRCA2 either do not exist, are rare, or are associated with low disease penetrance.

Adult↗
PubMedDate not supplied

Prevalence of family history of breast and ovarian cancer in a single primary care practice using a self-administered questionnaire.

Women at high risk of hereditary breast and/or ovarian cancer require specific management strategies for cancer prevention and early detection. The goal of this study was to determine the prevalence of familial breast and ovarian cancer among patients in a primary care practice. Questionnaires were mailed to the 608 women less than 81 years of age in a single primary care practice. Additional mailings and phone calls were used for nonresponders. Data were analyzed by bloodline, the degree of relative, age of diagnosis and cancer type. Women were grouped into three categories of breast/ovarian family history: "no family history,""insignificant family history," and "significant potentially high-risk family history" (women with two or more relatives in a single bloodline with breast and/or ovarian cancer, a single individual with bilateral breast cancer or breast and ovarian cancer, or breast and/or ovarian cancer at less than 40 years of age). A pedigree analysis of women categorized as "significant potentially high-risk family history" further classified these women as to the likelihood of being at risk for hereditary cancer. Data were obtained from 567 women (93%); 27 patients with a personal diagnosis of breast and/or ovarian cancer were excluded. Of the 540 remaining respondents, 351 (65%) had no family history of cancer, 138 (25.6%) had an insignificant family history, and 51 (9.4%) had a significant family history. Based on pedigree analysis of these 51 patients, 19 were unlikely to be at high risk for hereditary cancer, and 32 (6%) were likely to be at significant risk and warrant intensive evaluation. The large proportion of women identified with a significant family history of breast and/or ovarian cancer has major implications regarding the magnitude of a population-based process to identify and manage high-risk individuals.

Adult↗