Increased risk for atypical fractures associated with bisphosphonate use.

BACKGROUND: Studies suggest an increasing occurrence of atypical femoral fractures with the use of bisphosphonates. OBJECTIVE: To examine whether the use of bisphosphonates increases the risk for atypical fractures. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Literature search of MEDLINE, Embase and Cochrane CENTRAL (1948-June 2013). SELECTION CRITERIA: (i) randomized controlled trial or an observational study, (ii) evaluated bisphosphonate therapy versus no treatment and (iii) reported an incidence of subtrochanteric or diaphyseal fracture individually, or a composite of both. Two independent investigators completed study selection, data extraction and validity assessment. The Cochrane Risk of Bias Tool was used to assess the quality of included studies. RESULTS: Ten (n = 658497) studies were included in the meta-analysis which demonstrated a statistically significant increased risk of subtrochanteric or diaphyseal fracture with bisphosphonate use [adjusted odds ratios (AOR) = 1.99, 95% confidence intervals (CI)= 1.28-3.10] with I (2) = 84.3% (95% CI = 73.5%-89.5%) and Egger P = 0.01. Subtrochanteric fractures showed an AOR = 2.71 (95% CI = 1.86-3.95) with I (2) = 83.6% (95% CI = 64.3%-90.3%) and Egger's P = 2.29. Diaphyseal fractures had an AOR = 2.06 (95% CI = 1.70-2.50), I (2) = 29.7% (95% CI = 0%-73.7%) and Egger's P = 1.22. CONCLUSION: Results suggest there is an increased risk for atypical fractures associated with bisphosphonates and raises awareness to the potential complications related with bisphosphonates. These findings warrant the comprehensive evaluation of patients before initiating bisphosphonate therapy and highlights the need for additional medical decision analyses in future studies to compare the benefit over potential harms of bisphosphonate therapy.

Implementation of the National Breast and Cervical Cancer Early Detection Program: the beginning.

In 1990, Congress passed the Breast and Cervical Cancer Mortality Prevention Act because of increases in the number of low-income and uninsured women being diagnosed with breast cancer. This act authorized the Centers for Disease Control and Prevention (CDC) to establish the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) to provide high-quality and timely breast and cervical cancer screening and diagnostic services to low-income, uninsured women. The program started in 1991, and, in 1993, Congress amended the act to allow the CDC to fund American Indian and Alaska Native tribes and tribal organizations. By 1996, the program was providing cancer screening across the United States. To ensure appropriate delivery and monitoring of services, the program adopted detailed policies on program management, evidence-based guidelines for clinical services, a systematized clinical data system to track service quality, and key partnerships that expand the program's reach. The NBCCEDP currently funds 67 programs, including all 50 states, the District of Columbia, 5 US territories, and 11 tribes or tribal organizations.

Trends in endometrial cancer incidence by race and histology with a correction for the prevalence of hysterectomy, SEER 1992 to 2008.

BACKGROUND: Incidence rates of endometrial cancer are routinely calculated without removing women who have had a hysterectomy from the denominator, which leads to an underestimate. Furthermore, as the number of women who have had a hysterectomy (hysterectomy prevalence) varies by race, the estimate of racial difference in endometrial cancer incidence is incorrect. METHODS: Data from 1992 to 2008 from the SEER Program were used to calculate incidence rates of endometrial cancer (corpus uterus and uterus, NOS) for 67,588 women 50 years and older. Data from the Behavioral Risk Factor Surveillance System were used to estimate hysterectomy prevalence. SEER area populations were reduced by hysterectomy prevalence, and corrected incidence rates were calculated. RESULTS: For women 50 years and older, the corrected incidence rate of endometrial cancer was 136.0 per 100,000 among whites and 115.5 among blacks, a 73% and 90% increase respectively compared with the uncorrected rate. The increase was greater for black women because hysterectomy prevalence was higher among black women (47%) than white women (41%). The corrected incidence among black women significantly increased 3.1% per year compared with a 0.8% significant decrease among white women resulting in higher rates among black women toward the end of the study period. CONCLUSION: Correcting the incidence rate for hysterectomy prevalence provides more accurate estimates of endometrial cancer risk over time. IMPACT: Comparisons of rates of endometrial cancer among racial groups may be misleading in the absence of denominator correction for hysterectomy prevalence.

Endometrial cancer risk among younger, overweight women.

OBJECTIVE: To examine the risk for endometrial cancer among overweight women using the World Health Organization's clinical definitions of obesity based on body mass index (BMI). METHODS: Conducted in the early 1980s, the Cancer and Steroid Hormone study was a multicenter, population-based, case-control study of breast, ovarian, and endometrial cancers among women aged 20-54 years. Participants for the case group (n=421) were identified through cancer registries and had histologically confirmed endometrial cancer. Participants for the control group (n=3,159) were chosen by random-digit dialing methods in the same regions as those in the case group. Those in the case and control groups responded to the same questions during in-person interviews. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The relationship between endometrial cancer and BMI (calculated as weight [kg]/[height (m)]) was modified by age at last menstrual period (LMP). Of women who were younger than 45 years at LMP, those with BMIs of at least 35.0 had a greater risk of endometrial cancer (56%, 30/54) than did those with normal BMIs (4%, 59/1,492, adjusted OR 21.7, 95% CI 11.3-41.7). Of women age 45 or older at LMP, those with BMIs of at least 35.0 also had a greater risk (40%, 24/60) than did those with normal BMIs (14%, 168/1,235, adjusted OR 3.7, 95% CI 2.0-6.6). Women younger than 45 years at LMP and those with BMIs of at least 25.0 at 18 years and as adults (25%, 31/123) had an approximately sixfold increased risk (adjusted OR 5.8, 95% CI 3.4-9.8) compared with those with normal BMIs at 18 and as adults (4%, 58/1,460). CONCLUSION: Very obese women aged 20-54 years have an elevated endometrial cancer risk, which appears heightened by early menopause. LEVEL OF EVIDENCE: II.

Client-directed interventions to increase community demand for breast, cervical, and colorectal cancer screening a systematic review.

Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not all people who should be screened are screened, either regularly or, in some cases, ever. This report presents the results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other harms or benefits of interventions designed to increase screening for breast, cervical, and colorectal cancers by increasing community demand for these services. Evidence from these reviews indicates that screening for breast cancer (mammography) and cervical cancer (Pap test) has been effectively increased by use of client reminders, small media, and one-on-one education. Screening for colorectal cancer by fecal occult blood test has been increased effectively by use of client reminders and small media. Additional research is needed to determine whether client incentives, group education, and mass media are effective in increasing use of any of the three screening tests; whether one-on-one education increases screening for colorectal cancer; and whether any demand-enhancing interventions are effective in increasing the use of other colorectal cancer screening procedures (i.e., flexible sigmoidoscopy, colonoscopy, double contrast barium enema). Specific areas for further research are also suggested in this report.

Protection of mammography screening against death from breast cancer in women aged 40-64 years.

OBJECTIVE: This study assessed the efficacy of community-based screening mammography in protecting against breast cancer death, asking whether age differences in efficacy persisted in the 1990s. METHODS: In a case-control study with follow-up, odds ratios (OR) were used to estimate the relative mortality rates from invasive breast cancer among women with at least one screening mammogram in the two years prior to a baseline reference date compared to non-screened women, adjusting for potential confounding. The multicenter population-based study included 553 black and white women diagnosed during 1994-1998 who died in the following five years, and 4016 controls without breast cancer. RESULTS: Efficacy for reducing the rate of breast cancer death within five years after diagnosis was greater at ages 50-64 years (OR = 0.47, 95% confidence interval (CI) 0.35-0.63) than at ages 40-49 (OR = 0.89, 95% CI 0.65-1.23), and greater among postmenopausal (OR = 0.45, 95% CI 0.33-0.62) than premenopausal women (OR = 0.74, 95% CI 0.53-1.04). Estimates of efficacy were conservative, as shown by sensitivity analyses addressing whether cancer was discovered by a screening mammogram, age at which screening was received, the length of the screening observation window, and years of follow-up after diagnosis. CONCLUSIONS: Despite the persistence of age differences in efficacy of mammography screening, with greater observed benefit for women aged 50-64 years, these findings support current screening recommendations for women 40-64 years old.

Benefit of screening mammography in reducing the rate of late-stage breast cancer diagnoses (United States).

OBJECTIVE: We studied the benefit of modern mammography screening in community settings, evaluating age-related differences in rates of late-stage breast cancer detection. METHODS: Our multicenter population-based case-control study included 931 black and white women with incident breast cancer (American Joint Commission on Cancer Stage IIB or higher) diagnosed 1994-1998 and 4,016 randomly sampled controls never diagnosed with breast cancer. Adjusted odds ratios (ORs) estimated the relative rate of late-stage diagnosis in screened and non-screened women. RESULTS: Women aged 50-64 at diagnosis with at least one screening mammogram in the previous 2 years were significantly less likely to have late-stage diagnosis (OR = 0.41, 95% CI 0.33-0.52). Results for women aged 40-49 were consistent with a screening benefit, although the confidence interval marginally overlapped the null (OR = 0.81, 95% CI 0.64-1.02). Mammography screening was associated with lower rates of late-stage breast cancer among both premenopausal (OR = 0.64, 95% CI 0.50-0.81) and postmenopausal (OR = 0.44, 95% CI 0.35-0.56) women. CONCLUSIONS: With modern mammography in the community, rates of late-stage breast cancer diagnoses are lower in screened compared to non-screened women ages 40 and older, but age-related differences persist.

Breast cancer screening among low-income or uninsured women: results from the National Breast and Cervical Cancer Early Detection Program, July 1995 to March 2002 (United States).

OBJECTIVE: To describe the results of breast cancer screening among low-income and uninsured women in the only national organized screening program in the US, the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). METHODS: We analyzed mammography and diagnostic follow-up data for 789,647 women who received their first mammogram in the NBCCEDP and 454,754 subsequent mammograms among these women. We calculated the rate of mammograms with abnormal findings, diagnostic follow-up, biopsy, and cancers detected per 1000 mammograms by age and racial or ethnic groups. Positive Predictive Values (PPVs) were estimated for abnormal mammograms and biopsy. RESULTS: Nearly 64% of the women screened in the program were from 50 to 64 years of age and about 46% were members of racial or ethnic minority groups. Women aged 40 to 49 years had the highest rates of abnormal mammograms and of diagnostic follow-up. However, cancer detection rates were highest in women aged 60 to 64 years. In addition, the PPVs for both abnormal mammograms and biopsy were highest in the oldest age group. CONCLUSIONS: Cancer detection rates and PPVs for both abnormal mammograms and biopsy were highest in women aged 50 years or more. These results support the programs focus on screening women aged 50 and older for breast cancer.

Interventions to prevent skin cancer by reducing exposure to ultraviolet radiation: a systematic review.

The relationship between skin cancer and ultraviolet radiation is well established. Behaviors such as seeking shade, avoiding sun exposure during peak hours of radiation, wearing protective clothing, or some combination of these behaviors can provide protection. Sunscreen use alone is not considered an adequate protection against ultraviolet radiation. This report presents the results of systematic reviews of effectiveness, applicability, other harms or benefits, economic evaluations, and barriers to use of selected interventions to prevent skin cancer by reducing exposure to ultraviolet radiation. The Task Force on Community Preventive Services found that education and policy approaches to increasing sun-protective behaviors were effective when implemented in primary schools and in recreational or tourism settings, but found insufficient evidence to determine effectiveness when implemented in other settings, such as child care centers, secondary schools and colleges, and occupational settings. They also found insufficient evidence to determine the effectiveness of interventions oriented to healthcare settings and providers, media campaigns alone, interventions oriented to parents or caregivers of children, and community-wide multicomponent interventions. The report also provides suggestions for areas for future research.

Cervical screening in the National Breast and Cervical Cancer Early Detection Program, 1995-2001.

OBJECTIVE: To describe results of cervical cytology screening among low-income and uninsured women in the National Breast and Cervical Cancer Early Detection Program. METHODS: We analyzed data from 750,591 women who received their first Papanicolaou (Pap) test in the program between July 1995 and March 2001. RESULTS: Nearly 85% of the women were aged 40 years or older. Almost half were members of racial or ethnic minority groups. Overall, the percentage of abnormal Pap test results decreased with increasing age. The rates of cervical intraepithelial neoplasia (CIN) were highest in the younger age groups but the rate of invasive cancer increased with age. White women had the highest age-adjusted percentage of abnormal Pap test results and the highest rate of biopsy-confirmed CIN 2 or worse. CONCLUSIONS: In this nationwide screening program, only 7% of all biopsy-confirmed high-grade cervical lesions (CIN 2 or worse) were invasive cancer. This underscores the success of Pap screening in identifying preinvasive disease and preventing cancer. LEVEL OF EVIDENCE: II-3

Promoting informed decisions about cancer screening in communities and healthcare systems.

Individuals are increasingly involved in decisions about their health care. Shared decision making (SDM), an intervention in the clinical setting in which patients and providers collaborate in decision making, is an important approach for informing patients and involving them in their health care. However, SDM cannot bear the entire burden for informing and involving individuals. Population-oriented interventions to promote informed decision making (IDM) should also be explored. This review provides a conceptual background for population-oriented interventions to promote informed decisions (IDM interventions), followed by a systematic review of studies of IDM interventions to promote cancer screening. This review specifically asked whether IDM interventions (1) promote understanding of cancer screening, (2) facilitate participation in decision making about cancer screening at a level that is comfortable for individuals; or (3) encourage individuals to make cancer-screening decisions that are consistent with their preferences and values.Fifteen intervention arms met the intervention definition. They used small media, counseling, small-group education, provider-oriented strategies, or combinations of these to promote IDM. The interventions were generally consistent in improving individuals' knowledge about the disease, accuracy of risk perceptions, or knowledge and beliefs about the pros and cons of screening and treatment options. However, few studies evaluated whether these interventions resulted in individuals participating in decision making at a desirable level, or whether they led to decisions that were consistent with individuals' values and preferences. More research is needed on how best to promote and facilitate individuals' participation in health care. Work is especially needed on how to facilitate participation at a level desired by individuals, how to promote decisions by patients that are consistent with their preferences and values, how to perform effective and cost-effective IDM interventions for healthcare systems and providers and in community settings (outside of clinical settings), and how to implement these interventions in diverse populations (such as populations that are older, nonwhite, or disadvantaged). Finally, work is needed on the presence and magnitude of barriers to and harms of IDM interventions and how they might be avoided.

Risk of cervical cancer associated with extending the interval between cervical-cancer screenings.

BACKGROUND: Although contemporary guidelines suggest that the intervals between Papanicolaou tests can be extended to three years among low-risk women with previous negative tests, the excess risk of cervical cancer associated with less frequent than annual screening is uncertain. METHODS: We determined the prevalence of biopsy-proven cervical neoplasia among 938,576 women younger than 65 years of age, stratified according to the number of previous consecutive negative Papanicolaou tests. Using a Markov model that estimates the rate at which dysplasia will progress to cancer, we estimated the risk of cancer within three years after one or more negative Papanicolaou tests, as well as the number of additional Papanicolaou tests and colposcopic examinations that would be required to avert one case of cancer given a particular interval between screenings. RESULTS: Among 31,728 women 30 to 64 years of age who had had three or more consecutive negative tests, the prevalence of biopsy-proven cervical intraepithelial neoplasia of grade 2 was 0.028 percent and the prevalence of grade 3 neoplasia was 0.019 percent; none of the women had invasive cervical cancer. According to our model, the estimated risk of cancer with annual Papanicolaou tests for three years was 2 in 100,000 among women 30 to 44 years of age, 1 in 100,000 among women 45 to 59 years of age, and 1 in 100,000 among women 60 to 64 years of age; these risks would be 5 in 100,000, 2 in 100,000, and 1 in 100,000, respectively, if screening were performed once three years after the last negative test. To avert one additional case of cancer by screening 100,000 women annually for three years rather than once three years after the last negative test, an average of 69,665 additional Papanicolaou tests and 3861 colposcopic examinations would be needed in women 30 to 44 years of age and an average of 209,324 additional Papanicolaou tests and 11,502 colposcopic examinations in women 45 to 59 years of age. CONCLUSIONS: As compared with annual screening for three years, screening performed once three years after the last negative test in women 30 to 64 years of age who have had three or more consecutive negative Papanicolaou tests is associated with an average excess risk of cervical cancer of approximately 3 in 100,000.

Comparison of screening mammography in the United States and the United kingdom.

CONTEXT: Screening mammography differs between the United States and the United Kingdom; a direct comparison may suggest methods to improve the practice. OBJECTIVE: To compare screening mammography performance between the United States and the United Kingdom among similar-aged women. DESIGN, SETTING, AND PARTICIPANTS: Women aged 50 years or older were identified who underwent 5.5 million mammograms from January 1, 1996, to December 31, 1999, within 3 large-scale mammography registries or screening programs: the Breast Cancer Surveillance Consortium (BCSC, n = 978 591) and National Breast and Cervical Cancer Early Detection Program (NBCCEDP, n = 613 388) in the United States; and the National Health Service Breast Screening Program (NHSBSP, n = 3.94 million) in the United Kingdom. A total of 27 612 women were diagnosed with breast cancer (invasive or ductal carcinoma in situ) within 12 months of screening among the 3 groups. MAIN OUTCOME MEASURES: Recall rates (recommendation for further evaluation including diagnostic imaging, ultrasound, clinical examination, or biopsy) and cancer detection rates were calculated for first and subsequent mammograms, and within 5-year age groups. RESULTS: Recall rates were approximately twice as high in the United States than in the United Kingdom for all age groups; however, cancer rates were similar. Among women aged 50 to 54 years who underwent a first screening mammogram, 14.4% in the BCSC and 12.5% in the NBCCEDP were recalled for further evaluation vs only 7.6% in the NHSBSP. Cancer detection rates per 1000 mammogram screens were 5.8, 5.9, and 6.3, in the BCSC, NBCCEDP, and NHSBSP, respectively. Recall rates were lower for subsequent examinations in all 3 settings but remained twice as high in the United States. A similar percentage of women underwent biopsy in each setting, but rates of percutaneous biopsy were lower and open surgical biopsy higher in the United States. Open surgical biopsies not resulting in a diagnosis of cancer (negative biopsies) were twice as high in the United States than in the United Kingdom. Based on a 10-year period of screening 1000 women aged 50 to 59 years, 477, 433, and 175 women in the BCSC, NBCCEDP, and NHSBSP, respectively, would be recalled; and for women aged 60 to 69 years, 396, 334, and 133 women, respectively. The estimated cancer detection rates per 1000 women aged 50 to 59 years were 24.5, 23.8, and 19.4, respectively, and for women aged 60 to 69 years, 31.5, 26.6, and 27.9, respectively. CONCLUSIONS: Recall and negative open surgical biopsy rates are twice as high in US settings than in the United Kingdom but cancer detection rates are similar. Efforts to improve US mammographic screening should target lowering the recall rate without reducing the cancer detection rate.

Risk factors for failure to detect a cancer during clinical breast examinations (United States).

BACKGROUND: Although clinical breast examinations (CBEs) provide important opportunities to detect breast cancer, little is known about factors that affect cancer detection during CBEs performed in community settings. To evaluate several potential factors, we analyzed data from 1,056,153 cancer screening records reported to the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). METHODS: Using case-series methods, we compared 2159 cancers missed during CBEs with 3161 cancers detected during CBEs. Cancers missed during CBE were found by mammography and confirmed by biopsy or fine needle aspiration. RESULTS: After controling for cancer stage, tumor size, and breast symptoms at time of CBE, we found that patient age and CBE history were significantly associated with the likelihood of cancer detection. Compared to women 50-59, women 40-49 were more likely to have their cancer detected during CBE (odds ratio (OR) = 1.84, 95% confidence interval (95% CI) 1.47-2.29), while women 70 and older were less likely to have it detected (OR = 0.74, 95% CI: 0.55-1.00). Among women receiving their first NBCCEDP-funded CBE, 67.5% had their cancer detected by CBE. Among women receiving their second or third CBE, the values were 59.3 and 48.8%, respectively. In an adjusted logistic model, a significant inverse relationship was observed between number of prior CBEs and percent of cancers detected in the index CBE (OR = 0.79, 95% CI: 0.72-0.88). CONCLUSIONS: Among women diagnosed with breast cancer, older women and those who have had multiple CBEs were more likely to have their cancer missed during CBE.

Validation of self-reported screening mammography histories among women with and without breast cancer.

As part of a case-control study of the efficacy of screening mammography, the authors validated the mammography histories of 2,495 women aged 40-64 years with incident breast cancer diagnosed in 1994-1998 and a 25% random sample of 615 controls never diagnosed with breast cancer, all reporting a mammogram in the past 5 years. Subjects from five metropolitan areas of the United States were cross-classified by facility records ("gold standard") and self-report according to history of a recent screening mammogram (within 1 year or within 2 years). Sensitivity and specificity of self-reported screening at 1 year were 0.93 and 0.82, respectively, for cases and 0.92 and 0.80 for controls. At 2 years, sensitivity and specificity were 0.97 and 0.78 for both cases and controls. Confidence intervals for the differences in sensitivity and specificity were narrow and included zero. Scant evidence was found of telescoping (recollection of events as more recent than actual). Findings suggest that, in an interview-based case-control study of the efficacy of screening mammography, 1) estimated true prevalences of recent screening mammography adjusted for sensitivity and specificity will be slightly lower than self-reported prevalences, and 2) differential misclassification of exposure status is slight. Therefore, odds ratios will likely be biased toward the null, underestimating screening efficacy.

Building the infrastructure for nationwide cancer surveillance and control--a comparison between the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology, and End Results (SEER) Program (United States).

OBJECTIVE: In preparation for jointly publishing official government cancer statistics, the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI) compared incidence rates from NCI's Surveillance Epidemiology and End Results (SEER) Program and CDC's National Program of Cancer Registries (NPCR). METHODS: Data for 1999 covering 78% of the US population were obtained from SEER and selected NPCR registries that met high quality data criteria. Incidence rates (per 100,000 population) were age-adjusted to the 2000 US standard population, and 95% gamma confidence intervals were estimated. RESULTS: NPCR rates for all sites combined were higher than SEER rates (males: NPCR 553.6, SEER 538.7; females: NPCR 420.8, SEER 412.5), but rates for specific cancer sites varied by registry program. Rates for colon cancer (males: NPCR 47.0, SEER 42.7; females: NPCR 36.5, SEER 33.8) and tobacco-related cancers were higher in NPCR than SEER. In contrast, NPCR rates were lower than SEER rates for cancers of the female breast (NPCR 134.0, SEER 135.9), prostate (NPCR 162.0, SEER 170.2), and melanoma as well as for cancers more common among Asians and Pacific Islanders (e.g., stomach cancer). CONCLUSIONS: Rate differences may arise from population differences in socio-demographic characteristics, screening use, health behaviors, exposure to cancer causing agents or registry operations factors.