A multidisciplinary view of mastectomy and breast reconstruction: Understanding the challenges

The current review paper was written in collaboration with breast cancer surgeons from the European Breast Cancer Research Association of Surgical Trialists (EUBREAST), a breast pathologist from the Danish Breast Cancer Group (DBCG), and representatives from the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer course. Herein we summarize the different mastectomies and reconstruction procedures and define high-risk anatomical areas for breast cancer recurrences, to further specify the challenges in the surgical procedure, histopathological evaluation, and target volumes in case of postmastectomy irradiation, as recommended by the ESTRO guidelines according to the surgical procedure. The paper has original figures and illustrations for all disciplines for in-depth understanding of the differences between the procedures.     

Role of conservation therapy for invasive lobular carcinoma of the breast

Background: Invasive lobular carcinoma (ILC) accounts for 5% to 10% of all invasive breast cancers. Although breast conservation therapy using local excision and postoperative irradiation is a standard therapy for early invasive ductal breast cancer, the result of this strategy in ILC is not well documented. We sought to determine the rate of locoregional recurrence after breast conservation therapy in patients with ILC. Methods: A retrospective review of 74 patients with ILC treated with breast conservation therapy at The University of Texas M. D. Anderson Cancer Center (n=43) or The John Wayne Cancer Institute (n=31) between 1977 and 1993 was performed. Results: The median age of patients was 60 years, and median follow-up was 56 months (range 1 to 207 months). Thirty-nine patients had American Joint Committee on Cancer stage I disease, 30 had stage IIa disease, and five had stage IIb disease. All patients underwent surgical resection and postoperative radiation therapy. Twelve patients received postoperative adjuvant chemotherapy, and 27 patients were treated with adjuvant hormonal therapy. The 5-year actuarial locoregional recurrence rate was 9.8%, and the median time to recurrence was 77 months (range 41 to 113 months). Patients with positive or close (⩽1 mm) surgical margins were at increased risk for local recurrence on univariate analysis (p=0.034). Of the nine patients with breast recurrence, six underwent salvage therapy with total mastectomy and are disease free at the time of this writing, two patients died of distant disease, and one is alive with local disease at the time of this report. The 5-year disease-specific survival rate was 93.7%. Conclusions: Breast conservation therapy for ILC achieves locoregional control in the majority of patients. However, long-term follow-up of patients is important because many local recurrences following breast conservation therapy are late events. Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

乳腺癌新辅助化疗的现状与进展——南方乳腺癌论坛主要议题与共识

2018南方乳腺癌论坛于2018年12月21—12月22日在广州召开,大会针对目前乳腺癌新辅助化疗存在的诸多争议进行了广泛的交流与讨论,并达成了初步的共识。相信此次会议将对今后的相关临床工作提供帮助。     

Spatial Patterns of Breast Cancer Incidence and Uninsured Women of Mammography Screening Age

Breast cancer is the most common cancer and second leading cause of cancer mortality in women in the United States. Women who lack insurance have mammography screening rates that are suboptimal. Our objective was to spatially correlate incidence rates of breast cancer and uninsured women aged 40–64 years and identify outliers—areas where women may be underscreened due to poor access. The eight‐county consolidated metropolitan statistical area centered on Harris County, Texas was selected as the study region. Breast cancer incidence data from 1995 to 2004 were acquired from the State of Texas Cancer Registry as individual case data geocoded at the census tract level. A bivariate local indicator of spatial autocorrelation was used to evaluate the spatial pattern of breast cancer incidence and uninsured. Statistically significant negative spatial autocorrelation was observed between breast cancer incidence and uninsured status in women aged 40–64 (Moran's I ?0.2065, p < 0.001), indicating that as breast cancer incidence increased, uninsured rates decreased globally. Statistically significant local clusters of low breast cancer incidence and high incidence of uninsured were found. Future research is needed to assess mammography screening behaviors and barriers to screening at the local level.     

Effects of tamoxifen on growth and apoptosis of estrogen-dependent and -independent human breast cancer cells

Background: Apoptosis (“programmed cell death”) is an active process characterized by prominent nuclear changes and DNA cleavage, which distinguishes it from cellular necrosis. In this study we investigated whether tamoxifen (TAM) treatment of estrogen receptor ER(+) MCF-7 and ER(-) MDA-231 human breast cancer cells resulted in cytotoxicity and cellular changes typical of apoptosis. Methods: Cytotoxicity was measured using a tetrazolium assay. Cellular morphologic changes were observed using transmission electron microscopy. DNA cleavage was assessed using 1.6% agarose gel electrophoresis and was also quantitated biochemically. Results: Exposure of cells to TAM for 24 h resulted in dose- dependent cytotoxicity, and MCF-7 cells were somewhat more sensitive to TAM. TAM induced chromatin condensation around the nuclear periphery in both cell lines, changes typical of apoptosis. TAM-induced cytotoxicity correlated with dose-dependent DNA cleavage, which showed the characteristic “internucleosomal ladder.” DNA cleavage occurred at a slightly lower TAM dose and occurred somewhat sooner in MCF-7 cells. TAM-induced DNA cleavage in MCF-7 cells was inhibited by the protein synthesis inhibitor cycloheximide, the RNA synthesis inhibitor actinomycin D, and by 17β-estradiol. However, in MDA-231 cells, DNA cleavage was inhibited by cycloheximide, partially but not significantly inhibited by actinomycin D, and not inhibited by 17β-estradiol. Conclusions: TAM induces typical apoptosis in ER(+) or ER (-) human breast cancer cells. TAM induction of apoptosis in MCF-7 cells involves the estrogen receptor, and requires the synthesis of new protein and mRNA. TAM induction of apoptosis in MDA-231 cells depends primarily on protein synthesis. TAM-induced cytotoxicity and DNA damage appear to be explained in part by the induction of apoptosis. Results of this study were presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–19, 1994     

TGFβ-1 regulation of VEGF production by breast cancer cells

Background: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. TGFβ-1 acts as an indirect angiogenic agent. Methods: VEGF and TGFβ-1 were measured in the serum of breast cancer patients and agematched controls and in tumor tissue of cancer patients by ELISA. VEGF protein and mRNA expression by breast tumor cell lines were examined, and the effect of TGFβ-1 on VEGF production in these cells was assessed. Results: VEGF levels were significantly higher (P=.03) in the serum of patients with breast cancer compared to age-matched controls. A positive correlation was found between serum (r=0.539) and tumor tissue (r=0.688) levels of VEGF and TGFβ-1. Metastatic MDA-MB-231 breast cancer cells produce more VEGF than do the primary BT474 cells. TGFβ-1 significantly (P<.05) increased production of VEGF. Conclusions: Breast cancer cells constitutively produce VEGF protein and mRNA. There is a relationship between VEGF and TGFβ-1 levels in breast cancer patients, and TGFβ-1 regulates VEGF expression by breast cancer cells. Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

Progress on BIG 1-02/IBCSG 27-02/NSABP B-37, a Prospective Randomized Trial Evaluating Chemotherapy after Local Therapy for Isolated Locoregional Recurrences of Breast Cancer

Background  The utility of chemotherapy for women who experience a locoregional recurrence after primary treatment of early breast cancer remains an open question. An international collaborative trial is being conducted by the Breast International Group (BIG), the International Breast Cancer Study Group (IBCSG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine the effectiveness of cytotoxic therapy for these patients, either alone or in addition to selective use of hormonal therapy and trastuzumab. Methods  The trial population includes women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery, but subsequently develop an isolated local and/or regional ipsilateral invasive recurrence. Excision of all macroscopic tumor without evidence of systemic disease is required for study entry. Patients are randomized to receive chemotherapy or no chemotherapy; type of chemotherapy is not protocol-specified. Radiation, hormonal therapy, and trastuzumab are given as appropriate. The primary endpoint is disease-free survival (DFS). Quality-of-life measurements are collected at baseline, and then at 9 and 12 months. The accrual goal is 977 patients. Results  This report describes the characteristics of the first 99 patients. Sites of recurrence at study entry were: breast (56%), mastectomy scar/chest wall (35%), and regional lymph nodes (9%). Two-thirds of patients have estrogen-receptor-positive recurrences. Conclusion  This is the only trial actively investigating the question of “adjuvant” chemotherapy in locally recurrent breast cancer. The case mix of accrual to date indicates a broad representation of this patient population.     

Validation of a Breast Cancer Nomogram for Predicting Nonsentinel Lymph Node Metastases After a Positive Sentinel Node Biopsy

Background Although completion lymph node dissection (CLND) is the standard of care for breast cancer patients with sentinel lymph node (SLN) metastases, the SLN is the only node with tumor in 40% to 60% of cases. To assist with decision-making regarding CLND, investigators at Memorial Sloan-Kettering Cancer Center devised and validated a nomogram for predicting the likelihood of non-SLN metastases. To assess the generalizable use of this nomogram, validation analysis was performed by using an external database. Methods Eight clinicopathologic variables for 200 consecutive breast cancer patients at the University of Texas M. D. Anderson Cancer Center with SLN metastases and CLND were entered into the nomogram. The accuracy of the nomogram to predict non-SLN metastases was assessed by the receiver operating characteristic (ROC) curve and linear regression analysis. The accuracy of the nomogram with touch-imprint cytology (TIC) as a substitute variable for frozen section was also evaluated. Results The linear correlation coefficient of the nomogram-predicted probabilities correlated with the observed incidence of non-SLN metastases for all patients (.97). The accuracy of the nomogram as measured by the area under the ROC curve was .71. When applied solely to patients who had TIC assessment of the SLN, the area under the ROC curve was .74. Conclusions This study validated the Memorial Sloan-Kettering Cancer Center breast cancer nomogram by using an external database. TIC seems to be an acceptable substitute for frozen section as a nomogram variable. The nomogram may help predict an individual’s risk of non-SLN metastases and assist in patient decision making regarding the benefit of CLND. Presented at the Annual Meeting of the Society of Surgical Oncology, Atlanta, Georgia, March 3–6, 2005.     

The effectiveness of the Gail model in estimating risk for development of breast cancer in women under 40 years of age

Epidemiologic studies have provided information on risk factors for breast cancer. Gail and associates identified five risk factors using the Breast Cancer Detection Demonstration Project (BCDDP) population and developed a model to calculate a composite relative risk (RR). This model is commonly used to counsel women regarding their risk for breast cancer and was used by the National Surgical Adjuvant Breast Project (NSABP) for eligibility for the Breast Cancer Prevention Trial. Because the BCDDP population was composed almost entirely of women 40 years of age or older, our purpose was to evaluate the effectiveness of the Gail model in estimating the risk of breast cancer for women under 40 in the clinical setting. The Gail risk factors were assessed for 124 patients under the age of 40 treated for either ductal carcinoma in situ (DCIS) or invasive breast cancer at the Lahey Hitchcock Medical Center between 1983 and 1995. The RR was calculated using the Gail model. For comparison, two cohorts of women under the age of 40 were used: 107 randomly selected patients who underwent a breast biopsy because of a benign condition and 129 nurses from our institution who responded to a questionnaire that included reproductive and family history information as used in the Gail model. The RR calculated was the RR that existed at the time of the surgical consultation for a suspicious breast lesion. The Tarone-Ware method was used to analyze statistical significance of differences between distribution. Contingency tables were analyzed using Miettinen's modification of Fisher's exact test. No differences were found between the median RR for all groups. Only 2 of the 124 patients with breast cancer had a RR of 5 or more (the RR required to enter the Breast Cancer Prevention Trial). The distribution of age at menarche (AGEMEN) was the same for each group. No difference was found for the distribution of age at first live birth (AGEFLB) between those with breast cancer and those with a benign biopsy or the control group. The number of breast biopsies (NBIOPS) was higher in patients with a benign breast biopsy. No difference was found in the distribution of number of first-degree relatives with breast cancer (NUMREL). Overall the Gail model failed to differentiate those women about to have cancer diagnosed from two control populations. The Gail model is not useful in identifying immediate risk of breast cancer in women under 40 and should not be used for that purpose.     

Survey of ASCO Members on Management of Sentinel Node Micrometastases in Breast Cancer: Variation in Treatment Recommendations According to Specialty

Background  American Society of Clinical Oncology (ASCO) guidelines recommend axillary dissection (ALND) as the primary treatment for sentinel node micrometastases (SNMM) in breast cancer. We hypothesized that variation exists in adherence to these guidelines and management of SNMM as a result of the medical specialty of the treating physician. Methods  A questionnaire was e-mailed to 2511 active members of ASCO who specialize in breast cancer and who are board certified in surgery, medical oncology, or radiation oncology. Questions covered treatment of SNMM and factors influencing clinical decisions. Survey responses were analyzed by the Kruskal–Wallis and Fisher’s exact test. Results  Of 612 questionnaires viewed by recipients, 537 (88%) were completed by 382 medical oncologists, 100 surgeons, and 55 radiation oncologists. Most (98.5%) regarded SNMM as clinically important. Unexpectedly, ALND for SNMM was recommended by only 23% of surgeons, 23% of medical oncologists, and 15% of radiation oncologists (no statistically significant intergroup difference). Factors identified as important in selecting patients for ALND were tumor size, age, tumor grade, lymphovascular invasion, and size of metastases. Most respondents in each specialty (89% overall) would consider adjuvant chemotherapy for primary tumors <1 cm if SNMM were present. Tumor size, age, size of metastases, estrogen receptor/progesterone receptor status, HER-2 neu status, and gene expression profile would influence this decision. Radiation oncologists (76%) were more likely than medical oncologists (57%) or surgeons (47%) to consider axillary radiation instead of ALND for SNMM (P = 0.0021). Conclusions  Guidelines recommending ALND for SNMM are not being followed by most of the ASCO members we surveyed. Poster presentation at the 2nd Annual Breast Cancer Symposium of the American Society of Clinical Oncology, September 5–7, 2008. Presented at the 62nd Annual Cancer Symposium of the Society of Surgical Oncology, Phoenix, Arizona, March 4–8, 2009.     

Preoperative Chemotherapy Decreases the Need for Re-Excision of Breast Cancers Between 2 and 4 cm Diameter

Introduction  It is accepted that preoperative chemotherapy can result in increased breast preservation for breast cancers greater than 4 cm. The benefits of preoperative chemotherapy are less clear, however, for patients who present with smaller tumors and are already candidates for breast-preserving surgery. The goal of this study is to assess the effect of preoperative chemotherapy on breast cancers between 2 and 4 cm diameter. Methods  A retrospective chart review was conducted of patients diagnosed with new breast cancer at the Yale-New Haven Breast Center for the years 2002–2007. Patients were included in the study if their breast cancer was between 2 and 4 cm and their initial surgical treatment had been completed. Patients with distant metastases were excluded. Results  There were 156 new cancers that met study requirements. Forty-seven patients underwent preoperative chemotherapy, and 109 patients had their surgery first, usually followed by chemotherapy. Initial surgery was lumpectomy for 31 out of 47 patients (66%) in the preoperative chemotherapy group compared with 62 out of 109 patients (57%) in the surgery group. For patients with lumpectomies, 2 out of 31 patients (6%) in the preoperative group had positive margins and required re-excision compared with 20 out of 62 patients (37%) in the surgery-first group (P < 0.01). Conclusions  We conclude that, for tumors between 2 and 4 cm, preoperative chemotherapy is associated with a significantly decreased rate of re-excision following lumpectomy. This not only results in fewer mastectomies, but also avoids the morbidity and inferior cosmetic results associated with a re-excision lumpectomy. Presented at the 61st Meeting of the Society of Surgical Oncology, March 13–16, 2008, Chicago, IL. Carla J. Christy is a Norma Lies Mitchell Interdisciplinary Breast Fellow funded by the Breast Cancer Alliance, Greenwich, CT.     

From adjuvant therapy to breast cancer prevention: BCPT and STAR

The continued widespread prevalence of breast cancer supports placing a high priority on research aimed at its primary prevention, particularly among women who are at increased risk for developing this disease. The suggestion of potential agents for the primary chemoprevention of breast cancer evolved out of the treatment setting. Extensive experience with tamoxifen, a first-generation selective estrogen receptor modulator (SERM) showing efficacy, first, in the treatment of advanced breast cancer and, subsequently, as adjuvant therapy for early stage disease established the safety of this agent. Cumulative data from multiple adjuvant studies documented the efficacy of tamoxifen in reducing second primary breast cancers in the contralateral breast, supporting its potential as a chemopreventive agent for breast cancer. The safety and second primary data on tamoxifen, together with extensive information on its pharmacokinetics, metabolism, and antitumor effects, as well as its potentially beneficial effects on lipid metabolism and osteoporosis, led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to select tamoxifen for testing in the first prospective randomized phase III trial of the efficacy of a chemopreventive agent for preventing breast cancer in women at increased risk of the disease. Accordingly, in 1992 the NSABP started the Breast Cancer Prevention Trial (P-1) in which 13,388 women > or = 35 years of age who were at increased risk of breast cancer according to Gail model risk factors [family history, age, and personal history (i.e., age at first birth, age at menarche, previous breast biopsies)] were randomized to tamoxifen 20 mg/day or placebo for 5 years. Through 69 months of follow-up tamoxifen reduced the risk of invasive breast cancer, primarily estrogen receptor-positive tumors, by 49% (two-sided p < 0.00001). Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided p < 0.002). In addition, tamoxifen reduced fractures of the hip, radius, and spine, but it had no effect on the rate of ischemic heart disease. As previously shown, the rates of endometrial cancer and vascular events increased with tamoxifen. With the P-1 results establishing tamoxifen as the standard of care for the primary chemoprevention of breast cancer in high-risk women, concern over the side effects of tamoxifen has prompted a continuing search for an agent that displays a more desirable efficacy/toxicity profile. Raloxifene, a second-generation SERM approved for the prevention of osteoporosis in postmenopausal women, displays antiestrogenic properties in the breast and possibly the endometrium, and estrogenic effects in the bone and on the lipid profile, suggesting it as a candidate for comparison with the chemopreventive standard, tamoxifen. Raloxifene will be compared to tamoxifen in an equivalency trial, the Study of Tamoxifen and Raloxifene (STAR) NSABP P-2, which began in July 1999 at almost 500 centers in North America. The plan is to randomize 22,000 postmenopausal women > or = 35 years of age at increased risk of breast cancer by Gail criteria to tamoxifen 20 mg/day or raloxifene 60 mg/day for 5 years. Study endpoints include invasive and noninvasive breast cancer, cardiovascular disease, endometrial cancer, bone fractures, and vascular events.     

ABC1 Consensus Conference - a German Perspective: First International Consensus Conference on Advanced Breast Cancer (ABC1), Lisbon, November 5, 2011

A group of German breast cancer experts (medical oncologists and gynaecologists) reviewed and commented on the results of the first international 'Advanced Breast Cancer First Consensus Conference' (ABC1) for the diagnosis and treatment of advanced breast cancer. The ABC1 Conference is an initiative of the European School of Oncology (ESO) Metastatic Breast Cancer Task Force in cooperation with the EBCC (European Breast Cancer Conference), ESMO (European Society of Medical Oncology) and the American JNCI (Journal of the National Cancer Institute). The main focus of the ABC1 Conference was metastatic breast cancer (stage IV). The ABC1 consensus is based on the vote of 33 breast cancer experts from different countries and has been specified as a guideline for therapeutic practice by the German expert group. It is the objective of the ABC1 consensus as well as of the German comments to provide an internationally standardized and evidence-based foundation for qualified decision-making in the treatment of metastatic breast cancer.     

The role of ovarian ablation in the management of breast cancer

Abstract: In recent years the role of ovarian ablation as a therapeutic modality not only in the prevention but also in the treatment of breast cancer has reemerged after its initial use more than a century ago. BRCA‐1 and BRCA‐2 mutation carriers have an 85% lifetime risk of developing breast cancer. Bilateral salpingo‐oophorectomy is effective in reducing the risk of developing breast cancer in both BRCA‐1 and BRCA‐2 mutation carriers by 50%. Tamoxifen reduces the risk of breast cancer in BRCA‐2 mutation carriers, but not in BRCA‐1 mutation carriers. Breast cancer arising in BRCA‐1 mutation carriers is often estrogen receptor (ER) negative, unlike breast cancer developing in BRCA‐2 mutation carriers. Sixty percent of premenopausal patients with breast cancer have ER‐positive disease and 25% of breast cancer patients are premenopausal at diagnosis. The Early Breast Cancer Trialists’ Collaborative Group review has shown ovarian ablation to be an effective adjuvant therapy for premenopausal breast cancer patients less than 50 years of age. But the Early Breast Cancer Trialists’ overview also shows the benefit of ovarian ablation is uncertain if these patients also receive chemotherapy. Does the overview underestimate the efficacy of ovarian ablation? Some patients in these trials were ER negative. Most women less than 50 years of age who receive adjuvant chemotherapy become menopausal. So there is a need to test ovarian function suppression in the group who can benefit, or in other words, those that remain premenopausal after chemotherapy and have endocrine responsive breast cancer.     

The effect of prior breast biopsy method and concurrent definitive breast procedure on success and accuracy of sentinel lymph node biopsy

Background It has been suggested that sentinel lymph node (SLN) biopsy for breast cancer may be less accurate after excisional biopsy of the primary tumor compared with core needle biopsy. Furthermore, some have suggested an improved ability to identify the SLN when total mastectomy is performed compared with lumpectomy. This analysis was performed to determine the impact of the type of breast biopsy (needle vs. excisional) or definitive surgical procedure (lumpectomy vs. mastectomy) on the accuracy of SLN biopsy. Methods The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study. Patients with clinical stage T1–2, N0 breast cancer were eligible. All patients underwent SLN biopsy and completion level I/II axillary dissection. Statistical comparison was performed by χ² analysis. Results A total of 2206 patients were enrolled in the study. There were no statistically significant differences in SLN identification rate or false-negative rate between patients undergoing excisional versus needle biopsy. The SLN identification and false-negative rates also were not statistically different between patients who had total mastectomy compared with those who had a lumpectomy. Conclusions Excisional biopsy does not significantly affect the accuracy of SLN biopsy, nor does the type of definitive surgical procedure. Presented at the 54th Annual Meeting of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Breast carcinoma metastatic to paranasal sinuses

Background. Breast cancer affects 150,000 women a year in the United States. Breast carcinoma that is metastatic to the paranasal sinus (PNS) is rare. A patient with breast cancer treated recently at the University of Texas M. D. Anderson Cancer Center developed bilateral metastasis to the ethmoid sinuses. This case prompted a review of the incidence of this disease, its treatment, and outcome. Methods. A review of the published reports dating back to 1939 of breast carcinoma that was metastatic to the PNS was performed. In addition, autopsy series in the breast oncology literature were reviewed for cases of breast carcinoma that was metastatic to the PNS. Results. From this review, we identified only eight cases of breast carcinoma that was metastatic to the PNS. All cases were unilateral and presented as mass lesions. Despite treatment, all patients died soon after diagnosis. Conclusions. We conclude that breast carcinoma metastatic to the PNS is rare and has been uniformly fatal because, as disseminated disease, it does not respond well to conventional systemic therapies. © 1995 Jons Wiley & Sons, Inc.     

Prospects for standardization of surgical treatment for breast cancer

Surgical treatment of breast cancer in general guided cancer surgery in the direction of extensive radical operations until two decades ago. More recently, the trend has been toward conservative, less-extensive surgery. Moreover, breast cancer has become a model case for establishing standardization of surgical care of cancer. The Japanese Breast Cancer Society issued "Guidelines for Breast-Conserving Therapy" in 1999, and the Clinical Research Group for Establishing Guidelines for Standardized Diagnosis and Treatment for Breast Cancer became active in 2002 under the auspices of the Ministry of Health, Welfare and Labor. There are several areas of controversy in terms of surgical care in breast cancer. Examples are yet-immature breast-conserving surgery which is performed with wide variations (15-90%) depending upon the institution, and sentinel lymph node biopsy which must await long-term results before being recognized as standard care. The installation of expensive diagnostic devices indispensable for standardized surgical care might not be necessary at each institution, and it must be noted that postoperative follow-up policies practiced in Japan differ greatly from those recommended by the American Society of Clinical Oncology. Despite the anticipated difficulties, a consensus on what constitutes standardized surgical treatment for breast cancer might be easily reached among breast cancer surgeons. However, it may be somewhat difficult to popularize the standardized surgical treatment among ordinary general surgeons in Japan, since there is a wide disparity in the level of clinical care offered by individual physicians and healthcare institutions. Standardization of medical care guided by the government is mainly designed to reduce healthcare costs, which is instrumental in eliminating unnecessary medical interventions and may in turn shed light on valuable medical care advances. This may be the moment for the Japanese Surgical Society and its members who practice life-saving surgery to lead a genuine national medical reformation.     

Molecular biomarkers for breast cancer prognosis: coexpression of c-erbB-2 and p53

OBJECTIVE: To assess the prognostic significance of molecular biomarkers, particularly c-erbB-2 and p53, through study of prospective clinical data and archival breast cancer tissues for women accrued to the Alabama Breast Cancer Project. SUMMARY BACKGROUND DATA: Defining molecular abnormalities in breast cancer is an important strategy for early detection, assessment of prognosis, and treatment selection. Evidence is strong that selective biomarkers, including c-erbB-2 and p53, have prognostic significance in breast cancer. Few studies have analyzed the prognostic significance of coexpression of biomarkers. METHODS: Study patients were those accrued to the Alabama Breast Cancer Project (1975-1978) who had archival breast cancer tissues available for analysis. Criteria for entrance into the Alabama Breast Cancer Project were T1-3 breast cancer with M0 status. Age, nodal status, and histologic grade were also documented. Patients were randomized to radical versus modified radical mastectomy, and node-positive patients were also randomized to adjuvant chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]) versus melphalan. Archival breast cancer tissues were studied for c-erbB-2, TGF-alpha, p53, cathepsin D, bcl-2, and estrogen and progesterone receptor expression using immunohistochemistry. Survival curves were developed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, multivariate analysis using a rank regression model. RESULTS: Three hundred eleven patients were accrued to the Alabama Breast Cancer Project, and paraffin-embedded breast cancer tissues for 90 patients were available for immunohistochemical analysis of molecular biomarkers. Univariate analysis showed nodal status, c-erbB-2 expression, and p53 expression to have prognostic significance. Coexpression of c-erbB-2 and p53 was also found to have prognostic significance by the log-rank test. Multivariate analysis showed T stage, nodal status, c-erbB-2 expression, and p53 expression to have independent prognostic significance. CONCLUSIONS: These data suggest that c-erbB-2 and p53 expression in breast cancer have prognostic significance. After median follow-up of 16 years, coexpression of c-erbB-2 and p53 may have more prognostic significance than traditional prognostic factors such as T stage and nodal status. Prospective study of large numbers of patients with breast cancer is encouraged to validate these findings.     

Tumor Location of the Lower-Inner Quadrant Is Associated with an Impaired Survival for Women With Early-Stage Breast Cancer

Background There is growing evidence that tumors of the inner quadrants (especially the lower-inner quadrant) metastasize more often to the internal mammary chain (IMC). As these metastases are not investigated, patients with lower-inner quadrant tumors have an increased risk of being under-staged and under-treated and may therefore have a higher risk of death from breast cancer. Methods We identified all 1522 women operated for stage I breast cancer between 1984 and 2002 recorded at the population-based Geneva Cancer Registry. We compared breast cancer mortality risk by tumor location with multivariate Cox regression analysis that accounted for all factors linked to tumor location and survival. Results Ten-year disease-specific survival was 93% (95%CI: 91–94%). Patients with breast cancer of the lower-inner quadrant (n = 118; 7.8%) had an importantly increased risk of dying of breast cancer compared to women with breast cancer of the upper-outer quadrant (multiadjusted Hazard Ratio: 2.3, 95%CI: 1.1–4.5, P = 0.0206). The over-mortality associated with this quadrant was particularly evident for tumors >10 mm (multiadjusted HR: 3.6, 95%CI: 1.6–7.9, P = 0.0016). There was no increased breast cancer mortality risk for tumors located in other quadrants. Conclusions Tumor location in the lower-inner quadrant is an independent and important prognostic factor of stage I breast cancer. Further research is needed to evaluate if the over-mortality of patients with stage I cancer of the lower-inner quadrant is indeed a result of under-treatment due to undetected IMC metastases. If so, patients with stage I breast cancer of the lower-inner quadrant are good candidates for systematic IMC investigation. Part of this study was presented as a poster at the 28^th San Antonio Breast Cancer Symposium, December 8-11, 2005.