Abstract: To identify the Breast Imaging Reporting and Data System magnetic resonance imaging (MRI) enhancement characteristics of ductal carcinoma in situ (DCIS). A retrospective review of consecutive patients who underwent breast MRI for newly diagnosed breast carcinoma prior to surgery was conducted. This yielded 381 lesions in 361 patients with pathologic confirmation of either DCIS alone, invasive carcinoma alone, or mixed invasive and in-situ disease. Presence or absence of a MRI lesion at the site of the documented carcinoma was recorded, and for all identified MRI lesions the Breast Imaging Reporting and Data System morphology patterns were recorded. MRI features of the different malignancy types were compared utilizing Fisher's exact tests; 64/381 (16.8%) lesions had DCIS, 101/381 (26.5%) had invasive carcinoma, and 216/381 (56.7%) had mixed invasive/in situ carcinoma. A MRI lesion corresponding to the known cancer was identified in 55/64 (85.9%) cases of DCIS, 98/101 (97.0%) cases of invasive carcinoma, and 212/216 (98.1%) cases of mixed invasive and in-situ carcinoma. For pure DCIS lesions, 38/64 (59.4%) exhibited nonmass-like enhancement (NMLE), 9/64 (14.1%) were masses, and 8/64 (12.5%) were a focus. For pure invasive carcinomas 79/101(78.2%) were masses, 16/101 (15.8%) were NMLE, and 3/101 (3.0%) were a focus. For mixed lesions 163/216 (75.5%) were masses, 44/216 (20.4%) demonstrated NMLE, and 5/216 (2.3%) were a focus. The most common NMLE patterns of pure DCIS were segmental distribution and clumped internal enhancement. Although there is overlap in the MRI morphology and enhancement pattern of in situ and invasive breast carcinoma, DCIS more frequently manifests as NMLE than does invasive carcinoma.

Abstract: The purpose of this study was to evaluate the role of adjuvant chemotherapy in malignant phyllodes tumors of the breast treated at the Instituto Nacional de Cancerologia of Mexico. Twenty-eight patients with malignant phyllodes tumors of the breast enrolled in a observational study from January 1993 to December 2003 to receive four cycles of adjuvant chemotherapy with doxorubicin 65 mg/m(2) over 48 hours intravenous infusion and dacarbazine 960 mg/m(2) over 48 hours intravenous infusion (n = 17) versus observation (n = 11). All patients had surgical resection, and 38% had an axillary dissection. Seven patients (25%) received adjuvant radiotherapy. Log-rank test was used to test for differences in recurrence-free survival (RFS). The median patient age was 42 years (range, 23-76 years). The median tumor size was 13 cm (range, 3-30 cm), and 46% of the tumors were in the left breast. At a median follow-up of 15 months (range, 2-81 months), there were seven recurrences and five deaths. The 5 year RFS rate was 58% (95% CI = 36% and 92%) for the patients who received adjuvant therapy and 86% (95% CI = 63% and 100%) for the patients who did not (p = 0.17). The median survival after recurrence was 6.5 months. Adjuvant chemotherapy with doxorubicin and dacarbazine did not affect patient survival. Future studies to identify relevant molecular targets should be implemented in order to define effective therapies for phyllodes tumors of the breast.

Abstract: Histopathologic distinction between ductal and lobular carcinomas of the breast has been made since 1941. Together, these two subtypes account for >95% of all mammary carcinomas. With the recent advances in molecular techniques, our understanding of the biology behind these carcinomas has greatly expanded. The genomic aberrations in mammary carcinoma are highly complex and appear to be more associated with tumor grade rather than any histopathologic subtype. Protein and RNA expression profiling reveals a classification of mammary carcinoma that has some overlap with traditional histopathology and can at least partially explain clinical behavior. The goal of this review is to present what is currently known about the molecular profiles of infiltrating ductal and lobular carcinoma and how they relate to conventional histopathology and biologic behavior.

Abstract: HER2/neu is overexpressed in about 20% of invasive breast carcinomas. Numerous studies have shown that there is high level of concordance between the HER2/neu status of the primary breast cancer and the metastases of a given patient. Recently, changes in HER2/neu status with tumor progression have been reported, suggesting the possibility of an emerging different tumor clone. Little is known about intratumoral heterogeneity with regard to HER2/neu oncoprotein overexpression. We identified nine cases of invasive ductal carcinoma that showed intratumoral variation in HER2/neu oncoprotein expression by immunohistochemistry. This was confirmed by the intratumoral variation in the amplification status of the HER2/neu gene by fluorescence in situ hybridization and by chromogenic in situ hybridization. The results of this study suggest that some cases of primary breast carcinoma are heterogeneous in regard to HER2/neu gene amplification or protein overexpression. Heterogeneity of HER2/neu status in a tumor may be a rare event or underestimated. This phenomenon should be examined as it may contribute to a better understanding of the variation in therapeutic responses and the conflicting data in studies about the prognostic and predictive role of HER2/neu status in subsets of breast cancer patients.

Abstract: Women with benign breast diseases (BBD), particularly those with lesions classified as proliferative, have previously been reported to be at increased risk for subsequent development of breast cancer (BC). A cohort of 4970 women with biopsy-proven BBD, identified after histopathology review of BBD biopsies, was studied for determination of subsequent development of BC. We report on 4537 eligible women, 28% of whom are African-American, whose BBD mass was evaluable for pathologic assessment of breast tissue. Ascertainment of subsequent progression to BC from BBD was accomplished through examination of the tumor registries of the Henry Ford Health system, the Detroit SEER registry, and the State of Michigan cancer registry. Incidence rates (IR) are reported per 100,000 person years at risk (100 k pyr). Poisson regression models were used to evaluate the association of demographic and lesion characteristics with BC incidence, using person years at the time of BBD diagnosis as the offset variable. The estimated overall BC IR for this cohort is 452 (95% confidence interval [CI] = 394–519) per 100 k pyr. Incidence for women age 50 and older is 80% greater than for younger women (p = 0.007, IRR = 1.8, 95% CI = 1.36–2.36). Neither marital status (p = 0.91, IRR = 0.97, 95% CI = 0.73–1.29) nor race (p = 0.67, IRR = 0.9, 95% CI = 0.54–1.48) is associated with differences in BC IR. Compared with women having nonproliferative lesions, the risk for BC is greater for women with atypical ductal hyperplasia of (IRR = 5.0; 95%CI = 2.26–11.0; p < 0.001) and other proliferative lesions (IR = 1.7, 95% CI = 1.02–2.95; p = 0.04). BC risk for woman with atypical lesions is significantly higher than for women with proliferative lesions without atypia (IRR = 2.58, 95% CI = 1.35–4.90; p = 0.0039). Neither race nor marital status was a factor for BC incidence from BBD in this cohort. Age retained its importance as a predictor of risk. BBD lesion histopathology in the outcome categories of either proliferative without atypia or proliferative with atypia are significant risk factors for BC, even when adjusted for the influence of demographic characteristics. The risks associated with BBD histological classifications were not different across races.

Abstract: n Abstract: The purpose of this study was to compare the sensitivity and specificity of breast-specific gamma imaging (BSGI) using a high-resolution breast-specific gamma camera and magnetic resonance imaging (MRI) in patients with indeterminate breast findings. Twenty-three women with an indeterminate breast finding that required BSGI and MRI as deemed necessary by the interpreting radiologist or referring physician were included. MRI was performed on a GE 1.5T scanner and BSGI was performed on a Dilon high-resolution breast-specific gamma camera. All imaging findings were correlated with pathologic diagnosis. Thirty-three indeterminate lesions were evaluated in the study. There were a total of nine pathologically confirmed cancers. There was no statistically significant difference in sensitivity of cancer detection between BSGI and MRI. BSGI demonstrated a greater specificity than MRI, 71% and 25%, respectively. BSGI has equal sensitivity and greater specificity than MRI for the detection of breast cancer. n

Abstract: Path o 1 ogis ts: Darryl Carter, M.D., Yale University School of Medicine, New Haven, CT James Connolly, M.D., Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA Ian 0. Ellis, M.D., City Hospital NHS Trust, Nottingham, UK Vincenzo Eusebi, M.D., Universita di Bologna, Bologna, Italy Gerald C. Finkel, M.D., Jefferson Medical College, Philadelphia, PA Fred Gorstein, M.D., Jefferson Medical College, Philadelphia, PA Roland Holland, M.D., University Hospital Nijmegen, Nijmegen, The Netherlands

Abstract: Core needle biopsy (CNB) is used to sample both mammographically and ultrasound detected breast lesions. A diagnosis of ductal carcinoma in situ (DCIS) by CNB does not ensure the absence of invasive cancer upon surgical excision and as a result an upstaged patient may need to undergo additional surgery for axillary nodal evaluation. This study evaluates the accuracy of CNB in excluding invasive disease and the preoperative features that predict upstaging of DCIS to invasive breast cancer. Two hundred fifty-four patients over an 8-year period from 1994 to 2002 with a diagnosis of DCIS alone by CNB were retrospectively reviewed. Underestimation of invasive cancer by CNB was determined. Radiographic, pathologic, and surgical features of the cohort were compared using univariate and multivariate analysis. The mean age was 55 years (range 27-84) and mean follow-up was 25 months with one patient unavailable for follow-up. There were a total of six patient deaths, all of which were not disease-specific. A total of 21 out of 254 patients (8%) with DCIS by CNB were upstaged to invasive cancer following surgical excision. There was a significant inverse relationship between the number of core biopsies and the incidence of upstaging (p 0.4). Of 21 patients with invasion, all but two had comedonecrosis by CNB. Comedonecrosis by CNB significantly increased the likelihood of upstaging (p < 0.001). Of the 21 patients who were upstaged, 12 required subsequent surgery for nodal evaluation while nine had sentinel node biopsy at initial operation. Finally, upstaged patients were significantly more likely to have a positive margin (p < 0.008). Ductal carcinoma in situ with comedonecrosis on CNB can help to predict the possibility of invasion. Increasing the number of core biopsies reduced the likelihood of sampling error.

Abstract: To examine the role of health-related quality of life (HRQOL) in early treatment discontinuation among women enrolled in a breast cancer clinical trial. A total of 464 women were enrolled in the Eastern Cooperative Oncology Group randomized controlled trial of adjuvant regimens comparing six cycles of cytoxan, adriamycin and 5-flurouricil (5-FU) with a 16-week regimen (weekly therapy with cytoxan, adriamycin, vincristine, methotrexate, and 5-FU) among women with lymph node positive breast cancer. One hundred sixty-four women participated in the HrQL substudy using the Breast Chemotherapy Questionnaire, which was designed to measure HRQOL in women receiving chemotherapy. Changes in global HRQOL score were examined over time as a predictor of early treatment discontinuation using generalized estimation equations (GEE) modeling and Cox proportional hazards regression. We considered early treatment discontinuation as a longitudinal binary variable determined at each time point HRQOL was measured. The results of multivariate GEE model fitting indicated that declines in HRQOL (p=0.04), older age (p=0.02), higher degree of nausea (p=0.02), higher degree of neurosensory toxicity (0.03) and lower degrees of hair loss (p=0.004) were correlated with early treatment discontinuation. We then fitted a proportional hazard regression model for time to early discontinuation with HRQOL score as a time-dependent covariate. The results were identical. Declines in HRQOL during therapy predicted early treatment discontinuation even after accounting for age and chemotherapy-related side effects. In the age of ever more aggressive treatments for breast cancer, women's perception of the impact of these treatments on their lives will become more important.

Abstract: The purpose of this study was to determine whether there is a criterion that can be utilized to determine if excisional biopsy is indicated following the diagnosis of lobular neoplasia (LN) on core biopsy. Retrospective review of patient records with diagnosis of LN as highest risk diagnosis on core biopsy was performed. LN was defined to include both atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) and was categorized as focal or diffuse. The pathology was correlated with the mammographic finding to determine whether the diagnosis of LN was incidental or related to the mammographic finding. For those patients who did not undergo excision, follow-up data are presented along with treatment information. A total of 4,555 breast core biopsies were performed at our institution from January 1997 through March 2005. Of these, 35 patients were diagnosed with LN. Twenty six (74%) went on to excision and nine (26%) were followed. Biopsy was recommended for mammographically detected calcifications in the majority of cases. Twenty four (92%) of the 26 excised cases had focal LN and 2 of 26 (8%) had diffuse LN. Infiltrating lobular carcinoma was diagnosed in both cases of diffuse LN and no infiltrating carcinoma was seen when focal LN was diagnosed on core. Excision may not be necessary when a diagnosis of only focal LN is made on core biopsy. Diffuse LN may indicate an associated invasive cancer and should prompt excision.

Abstract: Metastases to the contralateral axillary lymph nodes in breast cancer patients are uncommon. Involvement of the contralateral axilla is a manifestation of systemic disease (stage IV) or a regional metastasis from a new occult primary (T0N1, stage II). The uncertain laterality of the cancer responsible for these metastases complicates overall disease staging and is a management dilemma for clinicians. Seven women who developed contralateral axillary metastases (CAM), but did not have evidence of systemic disease were identified. Patient demographics, histopathologic tumor characteristics, treatment and outcome were examined. The median age was 49 years. A family history of breast cancer was present in six (86%). The initial breast cancers were located in all quadrants. They were generally hormone receptor negative, HER-2/neu overexpressing and associated with lymphovascular invasion. There was a median interval of 71 months between initial breast cancer diagnosis and CAM presentation. Surgical management of the CAM included simple excision in one (14%) and axillary lymph node dissection in five (71%). Adjuvant treatment consisted of chemotherapy in seven (100%) and hormonal therapy in one (14%). The median follow-up from the diagnosis of CAM was 35 months and three women were alive without disease, two were alive with disease and two had died of disease. With surgical treatment, there were no axillary recurrences in this series. When patients present with CAM and no evidence of systemic disease or a new primary in the contralateral breast, surgical treatment should be considered for local control and possibly improved relapse-free survival.

Abstract: Tamoxifen has been the gold standard adjuvant therapy for the treatment of postmenopausal women with hormone-receptor-positive (HR+) early breast cancer for many years. Tamoxifen treatment is limited to 5 years because of the development of de novo and acquired resistance, and an ongoing risk of adverse events, including endometrial cancer, thromboembolic events, and gynecological symptoms with long-term use. The third-generation aromatase inhibitors (AIs), letrozole, anastrozole, and exemestane, are displacing tamoxifen as the first-choice therapy for HR+ early breast cancer, and are now recommended as the preferred therapy by national and international guidelines. Recent randomized trials have demonstrated that the AIs are more effective than tamoxifen in preventing disease recurrence when used in substitution and sequential strategies in the early adjuvant setting, and letrozole has been shown to be more effective than placebo in the extended adjuvant setting (after 5 years of tamoxifen therapy). Trial safety data show that the overall tolerability of AIs is similar to that of tamoxifen, with adverse events being predictably characteristic of estrogen deprivation; however, some important differences in adverse event profiles between tamoxifen and the AIs have been demonstrated. In addition to antiestrogenic effects, tamoxifen acts as an estrogen agonist in some tissues, which can lead to serious side effects not associated with the AIs, which prevent estrogen biosynthesis. A lower incidence of gynecological and thromboembolic events is observed in patients taking AIs, and fewer cases of endometrial cancer are seen compared with tamoxifen. Adverse events that are more frequent with adjuvant AI therapy compared with tamoxifen include arthralgia and myalgia, bone loss, and effects on the cardiovascular system and blood lipids. The effects of AIs on bone are predictable and may be easily managed, where necessary, with bisphosphonates. Studies examining the effects of AIs on the cardiovascular system and lipid profiles, including in the extended adjuvant setting, suggest that these adverse events may be due to the absence of a protective effect of tamoxifen rather than true AI toxicity. Further studies are required to determine the long-term safety of AI therapy in postmenopausal women with HR+ early breast cancer.

Abstract: This study aimed to determine the effects of demographic, clinical, and therapeutic variables in development of seromas. The relation between development of seromas and age, preference for surgery, tumor size, existence of axillary lymph nodes and lymph nodal metastases, number of lymph nodes removed, type of surgical equipments used, drainage duration, drainage flow rate, and whether or not neoadjuvant chemotherapy was received; dead volume was reduced; or pressure garment was used in patients who received surgery due to breast cancer between 2000 and 2005 years. Mean age of 119 patients included in the study was 53.13+/-13.26 (range 26-79). Seromas were observed in 17 (14.28%) patients. In multivariate logistic regression analysis an association of postoperative seroma formation was noted with a drainage flow rate greater than 50 mL/day after 48th hours following breast surgery (p=0.007), while other variables investigated herein are not associated with development of seromas. We conclude that a drainage flow rate greater than 50 mL/day after 48th hours is a predicting factor for seroma formation in breast cancer patients. Thus, we do not recommend terminating the drainage before flow rate at 48 hours is seen and daily drainage is lower than acceptable limit.

Abstract: Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferation of breast stromal cells with a complex pattern of interanastomosing spaces lined by myofibroblasts and is most commonly seen in women of child-bearing age. PASH is a frequent incidental microscopic finding in breast biopsies. Nodular PASH, however, resulting in a clinically appreciable mass and rapid growth is a rare entity, with only four such patients cited in the literature. Surgical excision results in a cure in the majority of cases, with a recurrence rate of approximately 7-22%. We report a case of a 12-year-old girl with nodular PASH who presented with bilateral breast enlargement refractory to surgical excisions, eventually requiring bilateral mastectomies. To our knowledge, our patient is the youngest patient to have nodular PASH and to undergo bilateral mastectomies.

Abstract: To identify factors that can influence breast edema in women undergoing breast-conserving therapy. Breast edema was assessed clinically and via high frequency ultrasound (HFUS) prior to, during and following radiotherapy. Fifty-four women were assessed. Breast edema was present prior to radiotherapy in patients who had undergone level 2 node dissection or had wound infection after sentinel node dissection. Edema increased during and after radiotherapy and peaked at 4–6 months. The time course of breast edema was related to the extent of nodal dissection, postoperative wound infection and regional radiotherapy. HFUS prior to irradiation was found to be no better than clinical assessment in predicting prolonged parenchymal breast edema but was significantly better at the end of irradiation. Breast edema levels are minimal in patients who do not undergo axillary node dissection or have an uncomplicated sentinel node dissection. Most edema is due to compromise of the draining lymphatics, which relates largely to the extent of axillary node dissection. HFUS appears to be a useful in the research setting in quantifying the effect of techniques that aim to reduce complications such as edema.

Abstract: The majority of women receiving breast augmentation surgery do so at a time in their lives when both reproduction and lactation are common. It does not occur to most women to consider the possible effects breast augmentation surgery may have on their future ability to exclusively breast-feed their baby. Most women raise concerns about their inability to exclusively breast-feed years after surgery when they have a child. It is therefore important that women considering breast augmentation surgery be fully informed of the possible effects surgery may have on their future ability to lactate. The possible direct effects of surgery on the breast tissue and the complications of breast surgery on future ability to lactate are discussed. Surgical technique, i.e., implant type and placement, are also discussed. The types of incisions made into the breast tissue and the positioning of the implants once inside the breast parenchyma are analyzed and their possible effects on future ability to lactate are explored. Women who undergo breast augmentation surgery have a greater incidence of lactation insufficiency. Factors directly related to the surgical procedure as well as short- and long-term complications of surgery compromise future ability to exclusively breast-feed a baby. Factors directly related to surgery include severing of the lateral and medial branches of the fourth intercostal nerve or the nerve endings of the nipple-areolar complex, which, lead to reduced sensation and loss of the suckling reflex resulting in decreased milk production. Hematoma formation increases the risk of developing capsular contracture therefore necessitating the need for further surgical intervention. Infection also requires further intervention and as a result, further risk to the breast tissue. Long-term breast pain, capsular contracture, and pressure effects on the breast from the implant are all possible long-term complications that compromise a woman's future ability to lactate and exclusively breast-feed her baby. With good surgical technique and proper postoperative management, most of the complications associated with surgery that may result in insufficient milk production can be minimized but not always avoided. Compared with nonaugmented women, women who have had augmentation surgery have a higher incidence of lactation insufficiency.

Abstract: Although breast reconstruction with deep inferior epigastric perforator (DIEP) flap is a well-described technique, few publications have specifically reported the technical aspects and the outcome following skin-sparing mastectomy (SSM). The aim of this study is to analyse the feasibility of its immediate application and to describe the operative planning, outcome and complications after SSM. 27 patients underwent 30 DIEP flap breast reconstructions with all immediate and 3 bilateral. Mean time of follow-up was 29 months. Breast skin, DIEP Flap and donor-site complications were evaluated. Information on patient satisfaction was collected. 70% had tumors measuring 2 cm or less (T1) and 74% were stage 0 and I according to American Joint Committee on Cancer. Breast skin complications occurred in 7.4%, all represented by small areas of skin necrosis. Partial losses were observed in two (7.4%) patients (less than 15% of total area) and total DIEP loss in 1 (3.7%). Donor-site complications represented by bulging occurred in only one patient (3.7%). The majority of patients were either very satisfied or satisfied. One local recurrence was observed. All complications except 2 were treated by a conservative approach. The DIEP flap is a reliable technique for SSM reconstruction. Success depends on patient selection, coordinated planning with the oncologic surgeon and careful intraoperative and postoperative management. The main advantage is that patients can safely undergo dual procedures with the added aesthetic benefits in breast and abdominal donor site.

Abstract: Increasing the number of breast cancer patients in follow-up involves increased costs and, with limited health care resources, there is a need to evaluate the cost-benefit to the patient of follow-up regimens. We present a randomized prospective study to evaluate the cost-benefit of intensive follow-up in the early detection of relapses in patients with breast cancer. One hundred and twenty-one patients were randomized to standard clinical follow-up (n=63) or to an intensive follow-up (n=58) that included diagnostic laboratory tests and imaging designed to detect early relapse following curative treatment. All patients had annual mammography. The number of scheduled outpatient appointments kept were 359 in the standard clinical follow-up and 355 in the intensive follow-up group. After a median of 3 years of follow-up, there were 28 relapses, 11 in standard clinical follow-up, and 13 in the intensive follow-up group. The overall cost of follow-up was 24,567 euros in the standard clinical follow-up group and 74,171 euros in the intensive follow-up group. Performing complimentary investigations in breast cancer follow-up is associated with higher costs without difference in early detection of relapses.

Abstract: We report a case of a 26-year-old woman with an 8.0-cm tumor of the left breast. The tumor was clinically and radiologically suspicious for malignancy. The pathologic evaluation of the core biopsy and the subsequent excision specimen revealed a benign sclerosing, cystic, and papillary adnexal tumor with apocrine and clear cell morphology. The immunohistochemical staining for p63 was positive. Estrogen, progesterone, and Her-2 receptor immunohistochemical stains were negative. The cytogenetic analysis revealed 46, XX t(11:19) (q21;q13.1) balanced translocation. The final diagnosis was apocrine hidradenoma.

Abstract: Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement in the same site. The occurrence of these tumors in the breast is extremely rare. Here, we present a case of a patient with both invasive ductal carcinoma and chronic lymphocytic leukemia in the breast. Wide excision with sentinel lymph node biopsy revealed palpably abnormal lymph nodes negative for breast carcinoma on frozen section. Histopathological examination of these lymph nodes showed extensive involvement by lymphoma and review of the breast specimen demonstrated the same lymphoma at the periphery of the ductal carcinoma. We review the literature and discuss possible etiologies for the dual presentation of both cancers.

Abstract: There is insurgence of literature evaluating prognostic and predictive factors in breast carcinomas treated with chemotherapy, with a parallel need to develop guidelines for the pathologist interpreting such excisions. Prechemotherapy gun biopsy and postchemotherapy excision specimens from 78 women with locally advanced breast cancer were analyzed for histological changes in the tumor, changes in the tumor grade, hormone receptors, cerb2, and bcl2 and their impact on disease-free survival (DFS). An unusually prominent granulomatous response to tumor was seen in three cases. The tumor grade changed in five patients, estrogen receptor (ER) expression was altered in 10 cases, progesterone receptor detection changed in 16 cases, cerb2 in one case and bcl2 in 16 cases. Fixation of the gun biopsy in Bouin's fluid and severe damage of nuclei after chemotherapy were the reasons for shift in the expression of hormone receptors. A low-grade tumor was associated with better response to chemotherapy. In the Kaplan-Meier analysis the ER expression and a low-grade tumor (grade I and II) significantly affected DFS. None of the factors evaluated impacted the overall survival of patients. To conclude there is a change in the tumor grade, bcl2, cerb2 and hormone receptors after chemotherapy. A pathologist interpreting specimens of breast cancer after chemotherapy must always record the postchemotherapy grade as it is an indicator of better response to chemotherapy and survival.

Abstract: The purpose of the study was to review the treatment outcomes of 198 patients treated with breast-conserving surgery (BCS) and whole breast radiation therapy using lung density correction for ductal carcinoma in situ (DCIS). Between April 1985 and December 2002, 198 patients with 200 lesions diagnosed as DCIS (AJCC stage 0) were treated at the University of Michigan. All underwent BCS and whole breast radiotherapy. Median total follow-up was 6.2 years (range: 0.8–18.2). The 5- and 10-year cumulative rates of in-breast only failure were 5.9% (95% CI: 2.6–9.3%) and 9.8% (95% CI: 5.2–14.4%), respectively. Factors that significantly predicted for an increased risk of local failure were family history of breast cancer, positive or close surgical margins and age ≤ 50 years at diagnosis. Cosmetic outcome was scored as “excellent” or “good” in 94% of the assessed patients. On multivariate analysis, only patient separation significantly predicted cosmetic outcome (p = 0.04). BCS and radiotherapy using lung density correction resulted in high rates of local control at 5 and 10 years with excellent cosmetic results. To the best of our knowledge, this is the first study to report outcome in a series of patients with DCIS treated with lung density correction and results compare favorably with other series in which plans were calculated using unit density.

Abstract: As breast cancer is the most frequent cancer in the elderly with a peak incidence of 1 in 10 by the age of 80, it is important to establish optimum therapy in this group. We conducted a case note-based retrospective study of all elderly primary breast cancer patients aged 80 and above between 1992 and 2002. The type of treatment, complications, disease progression, recurrence, and overall survival were recorded. In all 110 patients aged 80 and above were treated for primary breast cancer, with 32 patients having advanced disease. Of these, 62 patients received primary endocrine treatment. 48 patients underwent surgery with 30 patients undergoing mastectomy. At follow-up, 34 patients suffered disease progression in the primary endocrine treatment group and three patients had local recurrence in the surgical group. The Kaplan-Meier analysis revealed significantly better survival in the surgical treatment group when compared with the primary endocrine treatment group, both in the early disease (n = 41; median survival: 71 months; compared to n = 37; median survival: 42 months; p = 0.0002) and the advanced disease (n = 7; median survival: 48 months; compared to n = 25; median survival: 36 months; p = 0.03). Prompt surgery and adjuvant treatment can decrease relapse and improve survival even in patients older than 80 years.

Abstract: The purpose of this study was to evaluate the risk factors associated with supraclavicular nodal failure (SCF) in patients with one to three positive axillary nodes treated with breast conserving surgery and axillary dissection without supraclavicular node radiation (S/C RT) to aid in the selection of patients for S/C RT. Two hundred two breast conservation patients with one to three positive axillary nodes on axillary dissection treated with breast irradiation without S/C RT and 20 patients with S/C RT between August 1985 and May 2002 were identified and retrospectively evaluated. The Kaplan-Meier method was used to determine SCF-free and overall survival curves. Risk factors for SCF were examined. The median follow-up from surgery was 72 months (range: 4-195). Nine of 202 patients (4%) failed in the ipsilateral breast, 4 (2%) in the ipsilateral supraclavicular lymph nodes, 4 (2%) in the ipsilateral axillary and/or internal mammary nodes and 30 (15%) distantly. The 5- and 10-year SCF-free survival was 97.92%. The overall survival at 5, 10, and 15 years was 91.35%, 75.58%, and 67.18%, respectively. SCFs were associated with high grade or ER negative cancers, but not with number of positive nodes. Two of the four SCFs were associated with distant metastases, and two with local failures. One patient with a SCF was salvaged and is disease-free at 134 months. The overall low incidence of SCF in patients with one to three positive nodes treated with breast radiation alone after breast conserving surgery and adequate axillary dissection suggests that additional S/C RT is unnecessary in this cohort. When it occurs, supraclavicular nodal failure is often associated with distant metastases.

Abstract: With increased focus on quality assurance, a complete axillary lymph node dissection (ALND) has been defined as the removal of 10 or more lymph nodes (LN). The objective of this study was to determine which patient, physician, and geographic factors predict the adequacy of ALND in breast cancer patients. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multicenter, prospective study of 4,131 patients, all of whom had a sentinel node biopsy and completion ALND. Univariate and multivariate analyses were performed to determine which factors were independently associated with the removal of 10 or more LN. Of the 4,131 patients in this study, the median number of LN removed was 11 (range; 3-45). Ten or more LN were removed in 3,213 (77.8%) patients. The median patient age in this study was 60 (range; 27-100), with a median tumor size of 1.5 cm (range; 0.1-11.0 cm). On univariate analysis, patient age, tumor size, and palpability were correlated with adequacy of ALND. Academic affiliation and percentage of breast practice were significant physician factors predictive of adequacy of ALND. Both geographic region and community size were significantly correlated with adequacy of ALND. On multivariate analysis, patient age (p = 0.024), surgeon academic affiliation (p < 0.001), percentage breast practice (p < 0.001), and community size (p = 0.003) were significant determinants of adequacy of ALND. Younger patients were more likely to have an adequate ALND. Surgeons in academic practice had a higher rate of adequate ALND, as did those practicing in larger communities. Surgeons with a more breast experience had a lower rate of adequate ALND. Patient age, surgeon academic affiliation, and breast experience, as well as community size are all significant factors predictive of adequacy of ALND.

Abstract: Appropriate surgery in women with retroareolar breast cancer should allow resection of the cancer with wide free margins and an acceptable cosmetic result. The aim of this study was to compare breast conservation surgery (BCS) to mastectomy for treatment of retroareolar breast cancer. In a prospective nonrandomized study, 69 women with retroareolar breast cancers underwent either central quadrantectomy (n=33) with complete removal of the nipple-areola complex or mastectomy (n=36). Two of 33 (6%) patients scheduled for BCS had a secondary mastectomy and immediate reconstruction due to involved margins. After a median follow-up of 42 month (range 17-99 months) in the BCS group and 43 months (range 16-118 months) in the mastectomy group local and regional recurrences as well as systemic disease were comparable between both groups. The postoperative cosmetic result after BCS as evaluated by the patients was rated as excellent in 80% and good in 20% with no poor result. BCS followed by radiation therapy is a feasible alternative to mastectomy in patients with retroareolar breast cancer.

Abstract: The Van Nuys Prognostic Index 1996 (VNPI), based upon tumor size, pathological grade and tumor margins, is a guideline for the treatment of ductal carcinoma in situ (DCIS). It was thought to strongly decrease overtreatment. In 2003, age was added to the index as a fourth prognostic factor. We examined changes in treatment modality after applying the VNPI retrospectively and investigated if the addition of age to the Index causes a shift in treatment. The influence of each prognostic factor on disease-free survival (DFS) was calculated. We performed a retrospective file study of DCIS patients treated between 1985 and 2003 at the University Hospital, Antwerp. Patients were assigned a Van Nuys Score 1996 and 2003. The influence of tumor size, pathological grade, tumor margins and age on DFS was calculated with the Kaplan-Meier method and the log-rank test. We identified 104 DCIS cases with a median follow-up of 36 months. Twelve patients showed recurrence (11.5%), of whom seven were invasive (58%). Seventeen of the 29 women diagnosed before 1997 were undertreated according to the VNPI 1996 and six of them showed recurrence. The remaining three recurrences were correctly treated. Seventy-five patients diagnosed after 1997 were all treated according to the VNPI 1996 and only three had a recurrence. The introduction of age caused no significant shift in treatment modalities. Significant differences in DFS were seen between large (>41 mm) and small ( 60 years) and young (<40 years) patients (p = 0.024) and Van Nuys Subgroup 2 and 3 (p = 0.04). Tumor margins and pathological grade showed no significant difference in DFS. The VNPI can be a useful tool in the treatment of DCIS. However, this Index is not evidence-based, using a relatively small retrospective series of patients. The validity of the modified VNPI must be prospectively confirmed with large numbers of DCIS patients.

Abstract: The purposes of the study are to evaluate the efficacy and safety of mirtazapine 30 mg/daily for 12 weeks to reduce hot flushes (HF) in women with previous breast cancer and to assess the influence of the same treatment on sleep quality and other menopausal symptoms. A prospective pilot trial was conducted in 40 breast cancer patients with at least seven HF per day. A HF diary was completed daily; sleep quality and other menopausal symptoms were assessed with the Pittsburgh Sleep Quality Index (PSQI), the Menopause Rating Scale (MRS) and the SF-36 Health Survey. Treatment was never started by 13 out of 40 patients (32.5%) and was interrupted by 7 out of 27 patients (25%) due to of the occurrence of side effects (mostly somnolence). In the remaining 20 patients who completed the three months treatment period, there was a 55.6% (p < 0.05) reduction in HF frequency and 61.9% (p < 0.05) reduction in HF score as compared to baseline. A significant reduction in the MRS score (32.8%; p < 0.05) was observed. Mirtazapine appears to be effective in reducing HF in breast cancer survivors. The more frequent side effect was somnolence. A sizeable compiliance problem has been observed due to the reluctance to take antidepressant drugs and to side effects.