The need for breast cancer screening in women undergoing elective breast surgery: an assessment of risk and risk factors for breast cancer in young women.

BACKGROUND: Given the 11% lifetime risk of breast cancer and increasing popularity of elective breast surgery, the role of preoperative screening begs further investigation. There are currently no guidelines that indicate which women younger than 40 years of age should be screened preoperatively. OBJECTIVES: A meta-analysis of studies regarding the odds ratio (OR) and relative risk ratio for breast cancer risk factors in women younger than 40 was completed. METHODS: Of a total of 240 results in the PubMed database for articles referencing breast cancer risk factors in young women, eight were selected for review. A total of 5381 patients were included in the studies in this meta-analysis; 26 risk factors were identified. A meta-analysis was performed to determine the OR of each specific risk factor, with a 95% confidence interval. RESULTS: The most significant risk factors were having a sister with breast cancer (OR, 11.66), having a first-degree relative with breast cancer (OR, 2.66), having a mother with breast cancer (OR, 2.31), never having breastfed (OR, 1.77), and having undergone a breast biopsy (OR, 1.66). From these data, the authors developed a clinical questionnaire to estimate the risk of breast cancer in young women. In addition, an algorithm was developed for preoperative breast cancer screening for women of all ages undergoing elective breast procedures. CONCLUSIONS: For women younger than 40, the preoperative risk assessment involves two steps. First, the possibility of existing breast cancer should be evaluated with a preoperative screening survey. Second, the patient's risk for future development of cancer should be assessed, with a focus on genetic mutations. Women older than 40 years of age should be stratified to receive either a preoperative mammogram or MRI. The clinical questionnaire and preoperative screening algorithm provide an evidence-based guideline on which to base the discussion with patients regarding preoperative breast cancer screening.

Incidence and time course of bleeding after long-term amenorrhea after breast cancer treatment: a prospective study.

BACKGROUND: The incidence of chemotherapy-induced amenorrhea (CIA) and the time to subsequent menstrual bleeding in premenopausal breast cancer patients treated with current standard chemotherapy regimens was examined. METHODS: Four hundred sixty-six women ages 20 to 45 years at the time of diagnosis of a stage I to III breast cancer were recruited between January 1998 and July 2002. Patients completed monthly bleeding calendars from the time of study recruitment. Updated medical history data were obtained at 6-month intervals. RESULTS: Most women received doxorubicin and cyclophosphamide (AC); doxorubicin, cyclophosphamide, and paclitaxel (ACT); or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). Approximately 41% of women experienced an initial 6 months of CIA, and an additional 29% had at least 1 year of CIA. Approximately half of the women with 6 months of CIA and 29% of those with 1 year of CIA resumed bleeding within the subsequent 3 years, usually in the year after their amenorrheic episode. Resumption of bleeding differed significantly by treatment regimen after 6 months of CIA (P = .002; 68% with AC, 57% with ACT, and 23% with CMF), but not after 1 year of CIA (P = .5). Of the 23% of women who experienced an initial 2-year period of CIA, 10% resumed bleeding within the ensuing 3 years after their amenorrheic episode, but none had regular menses. CONCLUSIONS: A considerable proportion of women treated with chemotherapy will experience periods of CIA, but many will resume bleeding. Newer treatment regimens such as ACT appear to have a higher resumption of bleeding compared with CMF. This finding may have implications for choice of anti-estrogen treatment and for future potential pregnancies/fertility.

A fire in our hearts: passion and the art of surgery.

BACKGROUND: Surgery is a profoundly exciting and rewarding profession, so it is alarming to see a diminishing of passion for the field in the trainees that are now coming through our doors. The attrition rate of surgical residents is unacceptably high, especially when compared with other fields. METHODS: To investigate potential causes behind the current high attrition rates seen in general surgery residency programs. Medline was searched (January 1990 to November 2009). The Internet was searched (Google) for informational sites, newsletters, and informally published articles. RESULTS: Attrition rates in general surgery residency programs are > or =20%, and many residents withdrawing from the programs go to other fields. The implementation of the 80-hour work week, while reported to improve quality of life, has not reduced attrition rates, presumably because the same amount of material needs to be learned in what is now a shorter period of time. The use of physician extenders to relieve residents of routine floor work that does not contribute to residency training is one solution. Another is the reformulation of clinical duties to make time use more efficient. Most importantly, recruitment should be restricted to those students with the intellectual, physical, behavioral, and emotional traits that make them suitable for the field of surgery. CONCLUSIONS: Attrition rates from general surgery residencies may be reduced by increasing the efficiency of the training programs to optimize time use. Recruitment should target those students who have, or who are most likely to develop, a passion for the art of surgery.

Changes in female support network systems and adaptation after breast cancer diagnosis: differences between older and younger patients.

PURPOSE: This study evaluates the changes in social networks of older and younger breast cancer patients over a 6-month period following their first diagnosis and how such modifications are associated with changes in the patients' mood state. DESIGN AND METHODS: Newly diagnosed breast cancer patients were interviewed shortly after their diagnosis and again 6 months later. Female support network members enumerated by patients were interviewed once within 3 months of the patients' initial interview. RESULTS: Findings based on information for 149 network members of 26 patients indicate that members in older (> or =51 years) patients' networks were less likely to be dropped at follow-up (odds ratio [OR] = 0.21, p = .04) compared with those in younger patients' networks. Network members who provided more support were less likely to be dropped by younger patients (OR = 0.42, p < .01). Decrease in network size was associated with decrease in mood disturbances among younger patients (Profile of Mood State-Bipolar: beta = 0. 35, p < or = .01). IMPLICATIONS: Reducing the number of network members after cancer diagnosis may not necessarily lead to psychological distress, providing support for self-regulation of social network resources among cancer patients. Older patients' network members were more embedded in patients' networks, making it more stable over time. Identifying important network members (e.g., frequent support providers for younger patients and family members for older patients) and facilitating positive social interactions between these network members and patients may be beneficial.

Breast cancer management: the road to today.

When Cancer began publishing in 1948, 1 of the first articles to appear was a review of sex hormones and advanced carcinoma of the breast. Because little was then known about the biology of breast cancer, standard treatment was characterized by radical and disfiguring surgery, often with only a limited effect on long-term outcomes. Several pivotal developments in the ensuing 60 years changed this picture dramatically. The large tumors that were common at initial presentation in 1948 became increasingly uncommon with the growing use of screening mammography. It was soon suggested that these smaller tumors could be successfully treated with more conservative surgery, especially with the addition of multidrug chemotherapy and hormonal therapy as adjuvant treatments. These revolutionary developments, which have allowed many women to remain free of disease for extended periods of time, were chronicled in landmark papers that appeared in Cancer: the first clinical trial to determine whether screening mammography would improve outcomes, the early small trials comparing less invasive surgery with Halsted's radical mastectomy, the initial National Surgical Adjuvant Breast Project trial testing the efficacy of triethylenethiophosphoramide in combination with radical surgery, and the first antiestrogen trials. These articles are extraordinary not only for breaking new ground in their respective technical areas, but also for the keen insights shown by the authors into what would become important in the future.

Expressive writing as a presurgical stress management intervention for breast cancer patients.

This study evaluated whether expressive writing (EW) was an effective stress management intervention for breast cancer patients. Women were recruited at the end of neoadjuvant chemotherapy and assigned to write about their cancer experience (EW group; n = 24) or neutral topics (neutral writing [NW] group; n = 25). Women were asked to write for 20 minutes a day for a total of four writing sessions that were completed over a 7-day period. Participants were reassessed approximately 3 days before and 2 weeks after surgery. The intervention did not significantly decrease women's distress, perceived stress, sleep disturbance, or pain. There was some evidence that the EW group used more sleep medication at the presurgical assessment than the NW group. Social constraints moderated the effect of the intervention. Among women with high social constraints, the EW group reported lower average daily pain than the NW group. Among women with low social constraints, the EW group reported higher average daily pain than the NW group. EW was not broadly effective as a stress management intervention for women with breast cancer. These data do not support the use of EW as a presurgical mind-body complementary medicine program for this population.

Locoregional treatment outcomes after multimodality management of inflammatory breast cancer.

PURPOSE: The aims of this study were to determine outcomes for patients with inflammatory breast cancer (IBC) treated with multimodality therapy, to identify factors associated with locoregional recurrence, and to determine which patients may benefit from radiation dose escalation. METHODS AND MATERIALS: We retrospectively reviewed 256 consecutive patients with nonmetastatic IBC treated at our institution between 1977 and 2004. RESULTS: The 192 patients who were able to complete the planned course of chemotherapy, mastectomy, and postmastectomy radiation had significantly better outcomes than the 64 patients who did not. The respective 5-year outcome rates were: locoregional control (84% vs. 51%), distant metastasis-free survival (47% vs. 20%), and overall survival (51% vs. 24%) (p < 0.0001 for all comparisons). Univariate factors significantly associated with locoregional control in the patients who completed plan treatment were response to neoadjuvant chemotherapy, surgical margin status, number of involved lymph nodes, and use of taxanes. Increasing the total chest-wall dose of postmastectomy radiation from 60 Gy to 66 Gy significantly improved locoregional control for patients who experienced less than a partial response to chemotherapy, patients with positive, close, or unknown margins, and patients <45 years of age. CONCLUSIONS: Patients with IBC who are able to complete treatment with chemotherapy, mastectomy, and postmastectomy radiation have a high probability of locoregional control. Escalation of postmastectomy radiation dose to 66 Gy appears to benefit patients with disease that responds poorly to chemotherapy, those with positive, close, or unknown margin status, and those <45 years of age.

Mammography before diagnosis among women age 80 years and older with breast cancer.

PURPOSE: Screening mammography guidelines for patients age 80 years and older are variable. We determined the effect of mammography use on stage at breast cancer diagnosis and survival among women of this age range. PATIENTS AND METHODS: We used the linked Surveillance, Epidemiology, and End Results-Medicare database to evaluate 12,358 women >or= 80 years of age diagnosed with breast cancer between 1996 and 2002. Patients were grouped according to number of mammograms during the 60 months before diagnosis: nonusers (0 mammograms), irregular users (one to two mammograms), and regular users (three or more mammograms). Effects of mammography on disease stage (I to IIa v IIb to IV) and survival were determined by logistic regression and Cox proportional hazards analyses. RESULTS: Percentages of women with nonuse, irregular use, and regular use of mammography during the 5 years preceding diagnosis were 49%, 29%, and 22%, respectively. On multivariate analysis, patients were 0.37 times less likely to present with late-stage cancer for each mammogram obtained (odds ratio, 0.63; 95% CI, 0.63 to 0.67). Breast cancer-specific 5-year survival among nonusers was 82%, that among irregular users was 88%, and that among regular users was 94%. However, survival from causes other than breast cancer was also associated with mammography use, suggesting a bias for healthier patients to undergo mammography. CONCLUSION: Regular mammography among women >or= 80 years of age was associated with earlier disease stage, although improved survival remains difficult to demonstrate. Health care providers should consider discussing the potential benefits of screening mammography with their older patients, particularly for those without significant comorbidity.

Defining the clinical diagnosis of inflammatory breast cancer.

Inflammatory breast cancer (IBC) is an extremely aggressive disease that progresses rapidly and carries a very grim prognosis. It is characterized by erythema, rapid enlargement of the breast, skin ridging, and a characteristic peau d'orange appearance of the skin secondary to dermal lymphatic tumor involvement. Although a palpable tumor may not be present, about 55% to 85% of patients will present with metastases to the axillary or supraclavicular lymph nodes. Diagnosis of IBC is made on the basis of these clinical characteristics, as well as histopathologic verification of carcinoma. Accurate diagnosis is critically important, as multimodal therapy can significantly improve outcomes if instituted early enough.

Surgical management of inflammatory breast cancer.

Multimodality therapy consisting of primary chemotherapy, mastectomy, and radiotherapy appears to offer the most favorable outcomes for patients with inflammatory breast carcinoma (IBC). Patients who respond well to chemotherapy are the best candidates for surgery; if response to chemotherapy is poor, radiotherapy should be undertaken before attempting surgery. The operative field must be wide enough to encompass all secondary skin changes, and every attempt should be made to assure negative margins. Breast-conserving surgery and sentinel lymph node biopsy are not appropriate for patients with IBC. However, there are no medical contraindications to breast reconstruction after mastectomy, although most clinicians prefer to wait until after the completion of radiotherapy before attempting this additional surgery.

Timing of surgical intervention for the intact primary in stage IV breast cancer patients.

BACKGROUND: Recent studies demonstrate improved progression-free survival (PFS) and improved overall survival (OS) with extirpation of the primary tumor in breast cancer patients who present with metastatic disease at initial diagnosis. The subset of patients who would most benefit from surgery remains unclear. This study evaluates the pathological attributes and optimum timing for surgery in patients who present with stage IV breast cancer and an intact primary. METHODS: Retrospective, single-institution review of all breast cancer patients between 1997 and 2002 presenting with an intact tumor and synchronous metastatic disease. Information collected included: demographics, tumor characteristics, metastatic sites, type/timing of surgery, and radiation/systemic therapy received. Patients initiated treatment within 3 months of their diagnosis. Patients were divided into three groups based on time interval from diagnosis date to surgery date. Disease progression and vital status at last follow-up were evaluated. Analysis of metastatic PFS (defined by progression of systemic disease) benefit in relation to surgical timing was performed. RESULTS: Multivariate analysis revealed patients having only one site of metastasis, negative margins, and Caucasian race had improved PFS. Further analysis revealed non-Caucasian patients more often underwent surgical intervention for palliation versus surgery for curative intent, possibly explaining their worse outcome. Patients who underwent surgery in the 3-8.9 month or later period had improved metastatic PFS. CONCLUSIONS: Surgical extirpation of the primary tumor in patients with synchronous stage IV disease is associated with improved metastatic PFS when performed more than 3 months after diagnosis. Resection should be planned with the intent of obtaining negative margins.

Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged

The histone protein family member X (H2AFX) is important in maintaining chromatin structure and genetic stability. Genetic variants in H2AFX may alter protein functions and thus cancer risk. In this case-control study, we genotyped four common single nucleotide polymorphisms (i.e., -1654A > G [rs643788], -1420G > A [rs8551], and -1187T > C [rs7759] in the H2AFX promoter region and 1057C > T [rs7350] in the 3' untranslated region (UTR)) in 467 patients with sporadic breast cancer and 488 cancer-free controls. All female subjects were non-Hispanic whites aged T polymorphism. Therefore, we believe that H2AFX promoter polymorphisms may contribute to the etiology of sporadic breast cancer in young non-Hispanic white women. Larger association studies and related functional studies are warranted to confirm these findings.

Trends for inflammatory breast cancer: is survival improving?

The purpose of this study was to evaluate whether the survival of women with inflammatory breast cancer (IBC) treated at our institution has improved over the past 30 years. Three-hundred ninety-eight patients with IBC were treated between 1974 and 2005. Patient characteristics and outcomes were tabulated and compared among decades of diagnosis. Survival outcomes were estimated with the Kaplan-Meier product limit method and compared among groups with the log-rank statistic. Cox proportional hazards models were fit to determine the association between year of diagnosis and survival outcomes after adjustment for patient and disease characteristics and treatments received. The median follow-up was 5.8 years (range, 0.3-23.8 years). There were 238 recurrences and 236 deaths. The median recurrence-free survival (RFS) duration was 2.3 years and the median overall survival (OS) time was 4.2 years. In the models for RFS and OS, after adjustment for patient and disease characteristics, increasing year of diagnosis was not associated with a decrease in the risk for recurrence (hazard ratio, [HR], 1.00; 95% confidence interval [CI], 0.97-1.04) or death (HR, 0.97; 95% CI, 0.94-1.01). Our data show that there has not been an important change in the prognosis of patients with IBC in the last 30 years. Clinical trials focusing on the management of this aggressive disease are warranted. Disclosure of potential conflicts of interest is found at the end of this article.

Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy.

PURPOSE: To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response. PATIENTS AND METHODS: Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses. RESULTS: RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio = 2.50; 95% CI 1.70 to 3.69; P < .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort. CONCLUSION: RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.

Breast cancer vaccines: promise for the future or pipe dream?

The objective of this study was to review issues involved in the search for a breast cancer vaccine. A review of the recent literature (2004-2007) was undertaken, with earlier literature included as appropriate for background, to assess 1) current approaches being used to create a therapeutic breast cancer vaccine, and 2) potential strategies for a preventive vaccine targeting either an infectious agent or tumor-associated antigen. Several approaches to the development of a therapeutic vaccine show promise, including tumor cell/dendritic cell fusion and DNA vaccines based on single purified antigens or DNA fragments from whole cells. Most of these experimental vaccines have either not moved beyond preclinical testing or have not shown a significant clinical response. Strategies involving host factors that mitigate immune response against tumors also show promise. Interest has increased in developing a preventive vaccine that can be administered to immunocompetent patients with minimal or no evidence of disease. Prophylactic vaccines typically target infectious agents, but the evidence for an infectious etiology for breast cancer is largely descriptive and difficult to interpret. A second strategy for a preventive breast cancer vaccine is to target tumor-associated antigens. Ongoing clinical trials are utilizing this approach, with preliminary results that are encouraging.

Career satisfaction, practice patterns and burnout among surgical oncologists: report on the quality of life of members of the Society of Surgical Oncology.

BACKGROUND: Studies show that 30-50% of medical oncologists experience burnout, but little is known about burnout among surgical oncologists. We hypothesized that wide variation in burnout and career satisfaction exist among surgical oncologists. PATIENTS AND METHODS: In April 2006, members of the Society of Surgical Oncology (SSO) were sent an anonymous, cross-sectional survey evaluating demographic variables, practice characteristics, career satisfaction, burnout, and quality of life (QOL). Burnout and QOL were measured using validated instruments. RESULTS: Of the 1519 surgical oncologists surveyed, 549 (36%) responded. More than 50% of respondents worked more than 60 hours per week while 24% performed more than 10 surgical cases per week. Among the respondents, 72% were academic surgical oncologists and 26% spent at least 25% of their time to research. Seventy-nine percent stated that they would become a surgical oncologist again given the choice. Overall, 28% of respondents had burnout. Burnout was more common among respondents age 50 years or younger (31% vs 22%; P = .029) and women (37% vs 26%; P = .031). Factors associated with a higher risk of burnout on multivariate analysis were devoting less than 25% of time to research, had lower physical QOL, and were age 50 years or younger. Burnout was associated with lower satisfaction with career choice. CONCLUSIONS: Although surgical oncologists indicated a high level of career satisfaction, nearly a third experienced burnout. Factors associated with burnout in this study may inform efforts by program directors and SSO members to promote personal health and retain the best surgeons in the field of surgical oncology. Additional research is needed to inform evidenced-based interventions at both the individual and organizational level to reduce burnout.

Metastases to the breast from nonbreast solid neoplasms: presentation and determinants of survival.

BACKGROUND: Metastasis to the breast is rare, but it must be considered in the differential diagnosis of a breast mass. The purpose of this study was to identify clinical characteristics and outcomes associated with this entity to identify determinants of survival. METHODS: Between 1983 and 1998, 169 patients were confirmed by pathology to have metastasis to the breast from nonbreast solid organ primary tumors at University of Texas M. D. Anderson Cancer Center. Medical records were retrospectively reviewed for clinicopathological characteristics. Survival was determined by Kaplan-Meier analysis. RESULTS: The median age was 51 years (range, 13-85). One hundred forty-nine (88.2%) patients had a prior history of cancer. Ninety-one (53.9%) patients presented with additional systemic metastases. The most common histology identified was melanoma (65 patients, 38.5%). In most patients (77%), the diagnosis was initially made through physical examination. The median survival from the time the breast metastasis was diagnosed was 10 months (range, 0.4-192.7). On univariate analysis, a significantly better survival was observed in patients who had no evidence of other disease at the time of diagnosis (P = .0036), patients with neuroendocrine tumors (P = .023), and patients who underwent surgical resection for breast metastases (P = .0001). On multivariate analysis, patients who did not have surgery were 88% more likely to die than those who did (P < 0.001). CONCLUSIONS: Expected survival with metastasis to the breast is poor, therefore, local therapy should be tailored to each individual. The association between overall survival and surgical resection of metastases to the breast should be further investigated.

Overview of adjuvant systemic therapy in early stage breast cancer.

The benefits of adjuvant systemic therapy in reducing risk of distant relapse from breast cancer have been recognized for several decades. The intent of adjuvant therapy is to eliminate the occult micrometastatic breast cancer burden before it progresses into clinically apparent disease. Successful delivery of effective adjuvant systemic therapy as a complement to surgical management of breast cancer has contributed to the steady declines in breast cancer mortality observed internationally over the past 2 decades. Ongoing clinical and translational research in breast cancer seeks to improve the efficacy of systemic agents for use in the conventional postoperative (adjuvant) setting.