Ismail Jatoi

Male Breast Cancer: A Population-Based Comparison With Female Breast Cancer

PURPOSE Because of its rarity, male breast cancer is often compared with female breast cancer. PATIENTS AND METHODS To compare and contrast male and female breast cancers, we obtained case and population data from the National Cancer Institutes Surveillance, Epidemiology, and End Results program for breast cancers diagnosed from 1973 through 2005. Standard descriptive epidemiology was supplemented with age-period-cohort models and breast cancer survival analyses. RESULTS Of all breast cancers, men with breast cancer make up less than 1%. Male compared with female breast cancers occurred later in life with higher stage, lower grade, and more estrogen receptor-positive tumors. Recent breast cancer incidence and mortality rates declined over time for men and women, but these trends were greater for women than for men. Comparing patients diagnosed from 1996 through 2005 versus 1976 through 1985, and adjusting for age, stage, and grade, cause-specific hazard rates for breast cancer death declined by 28% among men (P = .03) and by 42% among women (P approximately 0). CONCLUSION There were three intriguing results. Age-specific incidence patterns showed that the biology of male breast cancer resembled that of late-onset female breast cancer. Similar breast cancer incidence trends among men and women suggested that there are common breast cancer risk factors that affect both sexes, especially estrogen receptor-positive breast cancer. Finally, breast cancer mortality and survival rates have improved significantly over time for both male and female breast cancer, but progress for men has lagged behind that for women.

Significance of Axillary Lymph Node Metastasis in Primary Breast Cancer

PURPOSE Axillary lymph node status is the single most important prognostic variable in the management of patients with primary breast cancer. Yet, it is not known whether metastasis to the axillary nodes is simply a time-dependent variable or also a marker for a more aggressive tumor phenotype. The purpose of this study was to determine whether nodal status at initial diagnosis predicts outcome after relapse and therefore also serves as a marker of breast cancer phenotype. PATIENTS AND METHODS Survival experience after first relapse in 1,696 primary breast cancer cases was analyzed using Cox proportional hazards regression. The following explanatory variables and their first-order interactions were considered: number of axillary lymph nodes involved (zero v one to three v four or more), hormone receptor status (any estrogen receptor [ER] negativity v ER negativity/progesterone receptor positivity v other ER positivity), primary tumor size (< 2 cm v 2 to 5 cm v > 5 cm), site of relapse (locoregional v distant), disease-free interval (< 1.5 years v 1.5 to 3 years v > 3 years), adjuvant endocrine therapy (none v any), adjuvant chemotherapy (none v any), and menopausal status (pre-, peri-, or postmenopausal). RESULTS Axillary lymph node status, site of relapse, and hormone receptor status were all highly significant as main effects in the model. After adjustment for other variables, disease-free interval alone was only modestly significant but interacted with nodal status. After disease-free interval, hormone receptor status, and site of relapse were accounted for, survival after relapse was poorer in node-positive cases, when compared with node-negative cases. The hazard ratios for patients with one to three and four or more involved nodes were 1.2 (95% confidence interval [CI], 0.8 to 1.9) and 2.5 (95% CI, 1.8 to 3.4), respectively. CONCLUSION Patients with four or more involved nodes at initial diagnosis have a significantly worse outcome after relapse than node-negative cases, regardless of the duration of the disease-free interval. We conclude that nodal metastasis is not only a marker of diagnosis at a later point in the natural history of breast cancer but also a marker of an aggressive phenotype.

Early breast cancer

Adoption of urbanised lifestyles together with changes in reproductive behaviour might partly underlie the continued rise in worldwide incidence of breast cancer. Widespread mammographic screening and effective systemic therapies have led to a stage shift at presentation and mortality reductions in the past two decades. Loco-regional control of the disease seems to affect long-term survival, and attention to surgical margins together with improved radiotherapy techniques could further contribute to mortality gains. Developments in oncoplastic surgery and partial-breast reconstruction have improved cosmetic outcomes after breast-conservation surgery. Optimum approaches for delivering chest-wall radiotherapy in the context of immediate breast reconstruction present special challenges. Accurate methods for intraoperative assessment of sentinel lymph nodes remain a clinical priority. Clinical trials are investigating combinatorial therapies that use novel agents targeting growth factor receptors, signal transduction pathways, and tumour angiogenesis. Gene-expression profiling offers the potential to provide accurate prognostic and predictive information, with selection of best possible therapy for individuals and avoidance of overtreatment and undertreatment of patients with conventional chemotherapy. Short-term presurgical studies in the neoadjuvant setting allow monitoring of proliferative indices, and changes in gene-expression patterns can be predictive of response to therapies and long-term outcome.

Randomized trials of breast-conserving therapy versus mastectomy for primary breast cancer : A pooled analysis of updated results

We have undertaken a pooled analysis of the 6 major randomized trials comparing mastectomy (MT) and breast-conserving therapy (BCT) in the treatment of primary breast cancer. Specifically, these trials compared the 2 most widely used options in local treatment: mastectomy and axillary dissection (MT) versus breast-conserving surgery, axillary dissection, and breast radiotherapy (BCT). The early results of these 6 trials formed the basis for a 1990 National Institutes of Health Consensus statement. However, most of these trials have recently published long-term follow-up results, and this pooled analysis incorporates the updated results of these 6 trials. For each of these trials, the observed number of treatment events was compared with that expected under the null hypothesis, given the number of patients per arm and the total number of events. Approximate odds ratios were computed using the observed and expected number of events, and the variance of the observed number of events. These were then pooled across trials to give overall odds ratios for the risk of locoregional recurrence, total recurrence, and death. Four of the 6 trials show that MT significantly reduces the risk of locoregional recurrence when compared with BCT, and the pooled odds ratio also shows a significant benefit for MT (odds ratio [OR], 1.561; 95% confidence interval [CI], 1.289–1.890; P <0.001). However, only 1 trial shows a statistically significant benefit for MT in reducing mortality, and the pooled odds ratio shows no significant difference between MT and BCT (OR, 1.070; 95% CI, 0.935–1.224; P = 0.33). This pooled analysis confirms that MT and BCT have comparable effects on mortality, even after long-term follow up. However, BCT is associated with a significantly greater risk of locoregional recurrence.

Why is breast-cancer mortality declining?

Population statistics indicate that age-adjusted breast-cancer mortality rates began to decline during the early 1990s in many developed countries. For several decades before 1990, breast-cancer mortality rates in these countries had been either stable or increasing. Many investigators attribute the decline in mortality to mammography screening. However, randomised prospective trials indicate that there is a delay of 10 years before the effect of such screening can be seen in mortality statistics. In many developed countries, screening programmes were launched in the late 1980s and early 1990s, so the sudden decline in breast-cancer mortality in the early 1990s was much too soon to be attributable to mammography screening. In this review, we argue that although some of the decline in breast-cancer mortality is due to a reduction in breast-cancer risk, most of it can probably be attributed to adjuvant systemic therapy and the earlier detection of palpable tumours. We also explain why advances in the treatment of breast cancer might be outpacing the value of mammography screening. Since age-adjusted mortality rates are the most basic measure of progress in the treatment of breast cancer, we suggest that careful scrutiny of recent trends in breast-cancer mortality may provide important insights into the effectiveness of novel strategies for diagnosis and treatment.

Breast Cancer Mortality Trends in the United States According to Estrogen Receptor Status and Age at Diagnosis

PURPOSE Since 1990, overall breast cancer mortality rates in the United States decreased 24%. This decline has been attributed to mammography screening and adjuvant systemic therapy. However, the efficacy of these modalities may depend on estrogen receptor (ER) expression and age. We therefore examined breast cancer mortality trends in the United States according to ER status and age. METHODS Using the Surveillance, Epidemiology, and End Results (SEER) program (1990-2003), we calculated trends in incidence-based mortality (IBM), annual hazard rates for breast cancer deaths after diagnosis, and relative hazard rates for women with ER-positive and ER-negative tumors. Relative hazard rates were assessed with Cox proportional hazards models, adjusted for stage and grade, and stratified by age at diagnosis. RESULTS During the study period, IBM and annual hazard rates for breast cancer deaths decreased among women with ER-positive and ER-negative tumors, although declines were greater for those with ER-positive tumors. Among women younger than 70 years, relative hazard rates declined 38% for those with ER-positive tumors versus 19% for those with ER-negative tumors. Among women 70 years or older, relative hazard rates declined 14% for those with ER-positive tumors versus no significant decline for those with ER-negative tumors. CONCLUSION In the United States, breast cancer mortality rates have declined among women with ER-positive and ER-negative tumors, with greater declines among younger women and those with ER-positive tumors. Although mortality in all groups remains unacceptably high, additional emphasis should be placed on improving outcomes of breast cancer patients older than 70 years and those of all ages with ER-negative tumors.

The global breast cancer burden.

Breast cancer now represents the most common female malignancy in both the developing and developed world, and is the primary cause of death among women globally. Despite well-documented reductions in mortality from breast cancer during the past two decades, incidence rates continue to increase and do so more rapidly in countries that historically had low rates. This has emphasized the importance of survivorship issues and optimal management of disease chronicity. This article reviews current trends of incidence and mortality in both a western and global context, and considers pertinent changes in underlying etiological risk factors. The latter not only offer clues regarding changes in incidence patterns, but also provides rationale and guidance for strategies that could potentially reduce the burden of this disease. The relevance of lifestyle adjustments and screening interventions for primary and secondary prevention, respectively, are discussed with reference to different healthcare resource settings.

Underlying Causes of the Black–White Racial Disparity in Breast Cancer Mortality: A Population-Based Analysis

BACKGROUND In the United States, a black-to-white disparity in age-standardized breast cancer mortality rates emerged in the 1980s and has widened since then. METHODS To further explore this racial disparity, black-to-white rate ratios (RRs(BW)) for mortality, incidence, hazard of breast cancer death, and incidence-based mortality (IBM) were investigated using data from the National Cancer Institutes Surveillance, Epidemiology, and End Results program on 244 786 women who were diagnosed with breast cancer from January 1990 through December 2003 and followed through December 2004. A counterfactual approach was used to examine the expected IBM RRs(BW), assuming equal distributions for estrogen receptor (ER) expression, and/or equal hazard rates of breast cancer death, among black and white women. RESULTS From 1990 through 2004, mortality RR(BW) was greater than 1.0 and widened over time (age-standardized breast cancer mortality rates fell from 36 to 29 per 100 000 for blacks and from 30 to 22 per 100 000 for whites). In contrast, incidence RR(BW) was generally less than 1.0. Absolute hazard rates of breast cancer death declined substantially for ER-positive tumors and modestly for ER-negative tumors but were persistently higher for blacks than whites. Equalizing the distributions of ER expression in blacks and whites decreased the IBM RR(BW) slightly. Interestingly, the black-to-white disparity in IBM RR(BW) was essentially eliminated when hazard rates of breast cancer death were matched within each ER category. CONCLUSIONS The black-to-white disparity in age-standardized breast cancer mortality was largely driven by the higher hazard rates of breast cancer death among black women, diagnosed with the disease, irrespective of ER expression, and especially in the first few years following diagnosis. Greater emphasis should be placed on identifying the etiology of these excess hazards and developing therapeutic strategies to address them.

Breast Cancer Trends Among Black and White Women in the United States

PURPOSE Overall US breast cancer mortality rates are higher among black women than white women, and the disparity is widening. To investigate this disparity, we examined incidence data and changes in mortality trends according to age, year of death (calendar period), and date of birth (birth cohort). Calendar period mortality trends reflect the effects of new medical interventions, whereas birth cohort mortality trends reflect alterations in risk factors. PATIENTS AND METHODS Incidence data were obtained from the Connecticut and National Cancer Institute Surveillance, Epidemiology, and End Results registries and mortality data were obtained from the National Center for Health Statistics. Changes in age, period, and cohort mortality trends were analyzed with Poisson regression. RESULTS For both races, breast cancer incidence rates for localized and regional disease diverged in the late 1970s. Almost concurrently, overall mortality rates diverged among blacks and whites. For both races, mortality increases with age, but blacks have higher mortality at age younger than 57. The calendar period curves revealed declining mortality for whites over the entire study period. For blacks, calendar period mortality declined until the late 1970s, and then sharply increased. After 1994, calendar period mortality declined for both. For women born between 1872 and 1950, trends in mortality were similar for blacks and whites. For women born after 1950, mortality decreased more rapidly for blacks. CONCLUSION The widening racial disparity in breast cancer mortality seems attributable to calendar period rather than birth cohort effects. Thus, differences in response or access to newer medical interventions may largely account for these trends.

Widening disparity in survival between white and African-American patients with breast carcinoma treated in the U. S. Department of Defense Healthcare system†

In the U. S., age‐adjusted breast carcinoma mortality rates among white and African‐American women have been diverging during the last 20 years. Some investigators speculate that the widening disparity is due to inequalities in access to healthcare, with African Americans having less access to necessary healthcare and improved therapies. Others argue that differences in tumor biology or some extrinsic influences on cancer etiology and behavior may account for the widening disparity. To examine this issue further, the authors compared trends in survival among white and African‐American women diagnosed with breast carcinoma in the U. S. Department of Defense (DoD), an equal access healthcare system.