Eliminating the breast cancer surgery paradigm after neoadjuvant systemic therapy: current evidence and future challenges.

In patients with operable early breast cancer, neoadjuvant systemic treatment (NST) is a standard approach. Indications have expanded from downstaging of locally advanced breast cancer to facilitate breast conservation, to in vivo drug-sensitivity testing. The pattern of response to NST is used to tailor systemic and locoregional treatment, that is, to escalate treatment in nonresponders and de-escalate treatment in responders. Here we discuss four questions that guide our current thinking about 'response-adjusted' surgery of the breast after NST. (i) What critical diagnostic outcome measures should be used when analyzing diagnostic tools to identify patients with pathologic complete response (pCR) after NST? (ii) How can we assess response with the least morbidity and best accuracy possible? (iii) What oncological consequences may ensue if we rely on a nonsurgical-generated diagnosis of, for example, minimally invasive biopsy proven pCR, knowing that we may miss minimal residual disease in some cases? (iv) How should we design clinical trials on de-escalation of surgical treatment after NST?

OncotypeDX Recurrence Score Does Not Predict Nodal Burden in Clinically Node Negative Breast Cancer Patients.

BACKGROUND: OncotypeDX recurrence score (RS)® has been found to predict recurrence and disease-free survival in patients with node negative breast cancer. Whether RS is useful in guiding locoregional therapy decisions is unclear. We sought to evaluate the relationship between RS and lymph node burden. METHODS: Patients with invasive breast cancer who underwent sentinel lymph node dissection from 2010 to 2015 were identified from a prospectively maintained database. Patients were excluded if they were clinically node positive or if they received neoadjuvant chemotherapy. RS was classified as low (< 18), intermediate (18-30), or high (> 30). The association between RS, lymph node burden, and disease recurrence was evaluated. Statistical analyses were performed in R version 3.4.0; p < 0.05 was considered significant. RESULTS: A positive SLN was found in 168 (15%) of 1121 patients. Completion axillary lymph node dissection was performed in 84 (50%) of SLN-positive patients. The remaining 84 (50%) patients had one to two positive SLNs and did not undergo further axillary surgery. RS was low in 58.5%, intermediate in 32.6%, and high in 8.9%. RS was not associated with a positive SLN, number of positive nodes, maximum node metastasis size, or extranodal extension. The median follow-up was 23 months. High RS was not associated with locoregional recurrence (p = 0.07) but was significantly associated with distant recurrence (p = 0.0015). CONCLUSIONS: OncotypeDX RS is not associated with nodal burden in women with clinically node-negative breast cancer, suggesting that RS is not useful to guide decisions regarding extent of axillary surgery for these patients.

Multidisciplinary Intraoperative Assessment of Breast Specimens Reduces Number of Positive Margins.

BACKGROUND: Successful breast-conserving surgery requires achieving negative margins. At our institution, the whole surgical specimen is imaged and then serially sectioned with repeat imaging. A multidisciplinary discussion then determines need for excision of additional margins. The goal of this study was to determine the benefit of each component of this approach in reducing the number of positive margin. METHODS: This single-institution, prospective study included ten breast surgical oncologists who were surveyed to ascertain whether they would have taken additional margins based their review of whole specimen images (WSI) and review of serially sectioned images (SSI). These results were compared with the multidisciplinary decisions (MDD) and pathology results. Margin status was defined using consensus guidelines. RESULTS: One hundred surveys were completed. Margins on the original specimen were positive or close in 21%. After WSI, surgeons reported that they would have taken additional margins in 26 cases, reducing the number of positive/close margins from 21 to 13% (p < 0.001). After SSI, 52 would have taken additional margins; however, the number of positive/close margins remained 13%. MDD resulted in additional margins taken in 56 cases, reducing the number of positive/close margins to 7% (p < 0.001 compared with SSI). CONCLUSIONS: While surgeon review of specimen radiographs can decrease the number of positive or close margins from 21 to 13%, more rigorous multidisciplinary, intraoperative margin assessment reduces the number of close or positive margins to 7%.

Baseline factors predicting a response to neoadjuvant chemotherapy with implications for non-surgical management of triple-negative breast cancer.

BACKGROUND: Patients with triple-negative breast cancer (TNBC) and a pathological complete response (pCR) after neoadjuvant chemotherapy may be suitable for non-surgical management. The goal of this study was to identify baseline clinicopathological variables that are associated with residual disease, and to evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal carcinoma in situ (DCIS) components in TNBC. METHODS: Patients with TNBC treated with neoadjuvant chemotherapy followed by surgical resection were identified. Patients with a pCR were compared with those who had residual disease in the breast and/or lymph nodes. Clinicopathological variables were analysed to determine their association with residual disease. RESULTS: Of the 328 patients, 36·9 per cent had no residual disease and 9·1 per cent had residual DCIS only. Patients with residual disease were more likely to have malignant microcalcifications (P = 0·023) and DCIS on the initial core needle biopsy (CNB) (P = 0·030). Variables independently associated with residual disease included: DCIS on CNB (odds ratio (OR) 2·46; P = 0·022), T2 disease (OR 2·40; P = 0·029), N1 status (OR 2·03; P = 0·030) and low Ki-67 (OR 2·41; P = 0·083). Imaging after neoadjuvant chemotherapy had an accuracy of 71·7 (95 per cent c.i. 66·3 to 76·6) per cent and a negative predictive value of 76·9 (60·7 to 88·9) per cent for identifying residual disease in the breast and lymph nodes. Neoadjuvant chemotherapy did not eradicate the DCIS component in 55 per cent of patients. CONCLUSION: The presence of microcalcifications on imaging and DCIS on initial CNB are associated with residual disease after neoadjuvant chemotherapy in TNBC. These variables can aid in identifying patients with TNBC suitable for inclusion in trials evaluating non-surgical management after neoadjuvant chemotherapy.

Breast conserving surgery and locoregional control after neoadjuvant chemotherapy.

The management of breast malignancy and the role of neoadjuvant systemic therapy has continued to evolve over the past 50 years. Survival equivalence with adjuvant systemic therapy is well accepted and demonstrated in several clinical trials. However, strong association with survival outcome and pathologic complete response emerged. Assessment of tumor response, as a surrogate for outcome, continues to be a driver for neoadjuvant therapy with increased applicability in the setting of sophisticated understanding and implications of breast tumor biology and molecular subtype. Furthermore, tumor response to neoadjuvant therapy can significantly impact local regional therapy decision-making by down-staging disease without compromising local regional control. This includes facilitation of breast conserving surgery and increased eligibility for limited axillary surgery in selected patients. Furthermore, the omission of surgery in the setting of exceptional response to neoadjuvant chemotherapy, the ultimate breast conserving strategy, is being actively studied. With further refinement of systemic and targeted therapies, neoadjuvant systemic therapy continues to provide a robust mechanism for innovation in local regional management paradigms with increased attention to individualized breast oncologic care.

Which threshold for ER positivity? a retrospective study based on 9639 patients.

BACKGROUND: Guidelines for the use of chemotherapy and endocrine therapy recently recommended that estrogen receptor (ER) status be considered positive if ≥1% of tumor cells demonstrate positive nuclear staining by immunohistochemistry. In clinical practice, a range of thresholds are used; a common one is 10% positivity. Data addressing the optimal threshold with regard to the efficacy of endocrine therapy are lacking. In this study, we compared patient, tumor, treatment and survival differences among breast cancer patients using ER-positivity thresholds of 1% and 10%. METHODS: The study population consisted of patients with primary breast carcinoma treated at our center from January 1990 to December 2011 and whose records included complete data on ER status. Patients were separated into three groups: ≥10% positive staining for ER (ER-positive ≥10%), 1%-9% positive staining for ER (ER-positive 1%-9%) and <1% positive staining (ER-negative). RESULTS: Of 9639 patients included, 80.5% had tumors that were ER-positive ≥10%, 2.6% had tumors that were ER-positive 1%-9% and 16.9% had tumors that were ER-negative. Patients with ER-positive 1%-9% tumors were younger with more advanced disease compared with patients with ER-positive ≥10% tumors. At a median follow-up of 5.1 years, patients with ER-positive 1%-9% tumors had worse survival rates than did patients with ER-positive ≥10% tumors, with and without adjustment for clinical stage and grade. Survival rates did not differ significantly between patients with ER-positive 1%-9% and ER-negative tumors. CONCLUSIONS: Patients with tumors that are ER-positive 1%-9% have clinical and pathologic characteristics different from those with tumors that are ER-positive ≥10%. Similar to patients with ER-negative tumors, those with ER-positive 1%-9% disease do not appear to benefit from endocrine therapy; further study of its clinical benefit in this group is warranted. Also, there is a need to better define which patients of this group belong to basal or luminal subtypes.

Pathologic complete response to neoadjuvant chemotherapy with trastuzumab predicts for improved survival in women with HER2-overexpressing breast cancer.

BACKGROUND: We sought to determine the prognostic value of pathologic response to neoadjuvant chemotherapy with concurrent trastuzumab. PATIENTS AND METHODS: Two hundred and twenty-nine women with HER2/neu (HER2)-overexpressing breast cancer were treated with neoadjuvant chemotherapy plus trastuzumab between 2001 and 2008. Patients were grouped based on pathologic complete response (pCR, n = 114) or less than pCR (

Six-year analysis of treatment-related toxicities in patients treated with accelerated partial breast irradiation on the American Society of Breast Surgeons MammoSite Breast Brachytherapy registry trial.

BACKGROUND: The American Society of Breast Surgeons (ASBrS) enrolled women in a registry trial to prospectively study patients treated with the MammoSite RTS device. This report presents 6-year data on treatment-related toxicities from the trial. METHODS: A total of 1449 primary early-stage breast cancers were treated with accelerated partial breast irradiation (APBI) using the MammoSite device (34 Gy in 10 fractions) in 1440 women. Of these, 1255 case (87%) had invasive breast cancer (IBC) (median size = 10 mm) and 194 cases (13%) had ductal carcinoma in situ (DCIS) (median size = 8 mm). Median follow-up was 59 months. Fisher exact test was performed to correlate categorical covariates with toxicity. RESULTS: Breast seromas were reported in 28% of cases (35.5% with open cavity and 21.7% with closed cavity placement). Also, 13% of all treated breasts developed symptomatic seromas, and 77% of these seromas developed during the 1st year after treatment. There were 172 cases (11.9%) that required drainage to correct. Use of chemotherapy and balloon fill >50 cc were associated with the development of symptomatic seromas. Also, 2.3% of patients developed fat necrosis (FN). The incidence of FN during years 1 and 2 were 0.9% and 0.8%, respectively. Seroma formation, use of hormonal therapy, breast infection, and A/B cup size were associated with fat necrosis. There were 138 infections (9.5%) recorded; 98% occurred during the 1st year after treatment. Chemotherapy and seroma formation were associated with the development of infections. CONCLUSIONS: Treatment-related toxicities 6 years after treatment with APBI using the MammoSite device are similar to those reported with other forms of APBI with similar follow-up.

Burnout and career satisfaction among surgical oncologists compared with other surgical specialties.

INTRODUCTION: Little is known regarding the rate of burnout, career satisfaction, and quality of life (QOL) among surgical oncologists compared with other surgical subspecialties. METHODS: The American College of Surgeons conducted a survey in 2008 involving 7,905 respondents, of whom 407 were surgical oncologists. Demographic variables, practice characteristics, career satisfaction, burnout, and quality of life (QOL) of surgical oncologists were compared with other surgical subspecialties using validated instruments. RESULTS: Surgical oncologists were younger (mean age 49.9 years), more likely to be female (26%), and had younger children than other surgical subspecialties. With respect to practice characteristics, surgical oncologists had been in practice fewer years and had fewer nights on call per week than other surgical disciplines but worked more hours (mean 62.6/week), were more likely to be in an academic practice (59.5%), were more likely to be paid on a salaried basis (68%), and had more time devoted to non-patient activities (e.g., research). Compared with surgeons from all other specialties, surgical oncologists had similar incidence of burnout (36%), suicide ideation (4.9%), and QOL, but lower incidence of depression (24%), and better indices of career satisfaction. CONCLUSIONS: These data provide a frame of reference for valid comparisons of burnout, QOL, and career satisfaction indices for the surgical oncology community relative to all other surgical specialties. Surgical oncologists have higher career satisfaction and lower risk of depression than surgeons in other surgical disciplines but still experience high rates of burnout.

The effect of under-treatment of breast cancer in women 80 years of age and older.

BACKGROUND: Several authors have demonstrated a trend toward the under-treatment of elderly and very elderly women with breast cancer. This study was undertaken to determine the impact of under-treatment of breast cancer in women age 80 and older. METHODS: A retrospective chart review of all patients 80 years and older with a newly diagnosed breast cancer at the MD Anderson Cancer Center, Houston, TX, between September 1, 1989 and September 1, 2004 was performed. Data extracted from charts included patient demographics, comorbidity, treatments recommended, treatments received, complications of therapy, disease recurrence and disease related death. Treatments undertaken were analyzed in the context of accepted therapy at the time of diagnosis. RESULTS: Two hundred twelve patients were identified. The median age was 83.5 years (range 80-97). Overall survival in the entire cohort was 7.28 years with a median follow up of 4 years for patients still alive at the end of the study period. Fifty seven percent of patients were under-treated according to institutional and national guidelines. Women who underwent hormonal therapy only demonstrated decreased disease specific survival (P<0.001 respectively) compared with patients who received multi-modality therapy. Women who underwent partial mastectomy without radiation treatment experienced a significant increase in local regional recurrence (P=0.045). There was an association of increased disease specific survival in patients who had surgical lymph node evaluation compared to those who did not (P=0.04). CONCLUSIONS: Outcomes are compromised in very elderly women with breast cancer in whom less than complete combined modality treatment is undertaken. With the previously demonstrated safety of radiation therapy, hormonal therapy and surgery in the very elderly population, multi-modality therapy should not be routinely withheld in patients in this age category.

Local control, toxicity, and cosmesis in women younger than 50 enrolled onto the American Society of Breast Surgeons MammoSite Radiation Therapy System registry trial.

BACKGROUND: The American Society of Breast Surgeons enrolled women onto a registry trial to prospectively study patients treated with the MammoSite Radiation Therapy System (RTS) breast brachytherapy device. This report examines local recurrence (LR), toxicity, and cosmesis as a function of age in women enrolled onto the trial. METHODS: A total of 1449 primary early-stage breast cancers were treated in 1440 women. Of these, 130 occurred in women younger than 50 years of age. Fisher's exact test was performed to correlate age (<50 vs. > or = 50 years) with toxicity and with cosmesis. The association of age with LR failure times was investigated by fitting a parametric model. RESULTS: Women younger than 50 were more likely to develop fat necrosis: 4.6% (6 of 130) vs. 1.8% (24 of 1319) (P = .0456). Other toxicities were comparable. At 2 years, cosmesis was excellent or good in 87% of assessable women aged <50 years (n = 74) and in 94% of assessable older women (n = 751) (P = .0197). At 3 years, this difference disappeared: excellent or good in 90% (56 of 62) of younger women vs. 93% (573 of 614) of older women (P = .2902). The crude LR rate for the group was 1.7% (25 of 1449). There was no statistically significant difference in LR as a function of age. In women <50, 3.1% (4 of 130) developed a LR; in the older patients, 1.6% (21 of 1319) developed LR (3-year actuarial LR rates, 2.9% vs. 1.7%, respectively; P = .2284). CONCLUSIONS: Accelerated partial breast irradiation with the MammoSite RTS results in low toxicity and produces similar cosmesis and local control at 3 years in women younger than 50 when compared with older women.

Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab.

BACKGROUND: The aim of this study was to compare the extent of pathologic response in patients with HER2-positive (HER2+) breast cancer treated with standard neoadjuvant chemotherapy, with or without trastuzumab (H), according to hormone receptor (HR) status. PATIENTS AND METHODS: We included 199 patients with HER2+ breast cancer from three successive cohorts of neo-adjuvant chemotherapy on the basis of paclitaxel (Taxol) (P) administered weekly (w) or three weekly (3-w), followed by 5-fluorouracil (F), doxorubicin (A) or epirubicin (E), and cyclophosphamide (C). Residual cancer burden (RCB) was determined from pathologic review of the primary tumor and lymph nodes and was classified as pathologic complete response (pCR) or minimal (RCB-I), moderate (RCB-II), or extensive (RCB-III) residual disease. RESULTS: In HR-positive (HR+) cancers, a higher rate of pathologic response (pCR/RCB-I) was observed with concurrent H + 3-wP/FEC (73%) than with 3-wP/FEC (34%, P = 0.002) or wP/FAC (47%; P = 0.02) chemotherapy alone. In HR-negative (HR-) cancers, there were no significant differences in the rate of pathologic response (pCR/RCB-I) from 3-wP/FAC (50%), wP/FAC (68%), or concurrent H + 3-wP/FEC (72%). CONCLUSIONS: Patients with HR+/HER2+ breast cancer obtained significant benefit from addition of trastuzumab to P/FEC chemotherapy; pathologic response rate was similar to that seen in HR-/HER2+ breast cancers.

Residual specimen cellularity after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Neoadjuvant chemotherapy for breast cancer reduces tumour cellularity, the percentage of the primary tumour area that is composed of invasive tumour cells. Minimal residual tumour cellularity (5 per cent or less of tumour area composed of invasive tumour cells) may be associated with an increased risk of false-negative intraoperative margins. The aim of this study was to evaluate the incidence of minimal residual tumour cellularity after neoadjuvant chemotherapy and its impact on the frequency of false-negative margins and conversion from breast-conserving surgery to mastectomy. METHODS: The final pathology slides of 510 patients who had surgery after neoadjuvant chemotherapy were reviewed. RESULTS: Of 396 patients with residual invasive breast cancer after neoadjuvant chemotherapy, 100 specimens (25.3 per cent) had minimal residual cellularity; this was more frequent in patients with invasive lobular carcinoma (17.0 versus 5.1 per cent; P < 0.001) or well and moderately differentiated carcinoma (68.0 versus 52.4 per cent; P = 0.007). Among 149 patients who had initial breast-conserving surgery, false-negative intraoperative margin rates were 23 per cent in specimens with minimal and 13.8 per cent in those with higher residual cellularity (P = 0.210). There was no significant difference in the rate of conversion to mastectomy between the groups. CONCLUSION: Minimal residual cellularity after neoadjuvant chemotherapy occurred in about 25 per cent of specimens, but did not alter the rate of false-negative intraoperative margins.

Inclusion of taxanes, particularly weekly paclitaxel, in preoperative chemotherapy improves pathologic complete response rate in estrogen receptor-positive breast cancers.

BACKGROUND: We examined if inclusion of a taxane and more prolonged preoperative chemotherapy improves pathologic complete response (pCR) rate in estrogen receptor (ER)-positive breast cancer compared with three to four courses of 5-fluorouracil, doxorubicin, cyclophosphamide (FAC). PATIENTS AND METHODS: Pooled analysis of results from seven consecutive neo-adjuvant chemotherapy trials including 1079 patients was carried out. These studies were conducted at MD Anderson Cancer Center from 1974 to 2001. Four hundred and twenty-six (39.5%) patients received taxane-based neo-adjuvant therapy. pCR rates and survival times were analyzed as a function of chemotherapy regimen and ER status. Multivariate logistic and Cox regression analysis were carried out to identify variables associated with pCR and survival. RESULTS: Patients with ER-negative cancer had higher overall pCR rate than patients with ER-positive tumors (20.1% versus 4.9%, P < 0.001). In ER-negative patients, the pCR rates were 29% and 15% with and without a taxane (P < 0.001). In ER-positive patients, the pCR rates were 8.8% and 2.0% with and without a taxane (P < 0.001). In multivariate analysis, clinical tumor size (P < 0.001), ER-negative status (P < 0.001) and inclusion of a taxane (P = 0.01) were independently associated with pCR. For patients with pCR, survival was similar regardless of ER status or the type of regimen that induced pCR. CONCLUSION: pCR rates increased for patients with both ER-positive and ER-negative tumors as regimens started to include a taxane and became longer. This indicates that a subset of patients with ER-positive breast cancer benefits from more aggressive chemotherapy, similarly to patients with ER-negative tumors.

Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer.

BACKGROUND: Women with breast cancer are more frequently being treated with preoperative neoadjuvant chemotherapy. The reliability of sentinel lymph node biopsy (SLNB) following chemotherapy has not been determined. This was a meta-analysis of studies that examined the results of SLNB after preoperative chemotherapy. METHODS: Included articles had to meet two criteria. First, patients had to have had operable breast cancer and to have undergone SLNB after preoperative chemotherapy and, second, patients had to have undergone subsequent axillary lymph node dissection. Meta-analyses were performed in which Bayesian hierarchical models were created to estimate the identification rate (IR) and sensitivity of SLNB in this setting. RESULTS: Twenty-one studies were identified that included a total of 1273 patients. The IRs reported ranged from 72 to 100 per cent, with a pooled estimate of 90 per cent. The sensitivity of SLNB ranged from 67 to 100 per cent, with a pooled estimate of 88 (95 per cent confidence interval 85 to 90) per cent. Meta-analyses performed using Bayesian modelling resulted in (posterior) estimates for IR and sensitivity of 91 (95 per cent credible interval 88 to 94) and 88 (95 per cent credible interval 84 to 91) per cent respectively. CONCLUSION: SLNB is a reliable tool for planning treatment after preoperative chemotherapy.

A single-gene biomarker identifies breast cancers associated with immature cell type and short duration of prior breastfeeding.

The pathogenesis of breast cancers that do not express estrogen receptors or Her-2/neu receptors (ER-/HER2- phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABA(A)) receptor subunit pi (GABApi, GABRP) in some breast cancers with ER-/HER2- phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide microarrays. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to measure GABApi gene expression in a separate cohort of 121 invasive breast cancers. GABApi gene expression values from TxP and RT-PCR were standardized and compared with clinicopathologic characteristics in the 203 patients. GABApi gene expression was increased in 16% of breast cancers (13/82 TxP, 20/ 121 RT-PCR), particularly in breast cancers with ER-/HER2- phenotype (60%), and breast cancers with basal-like genomic profile (60%). The profile of genes coexpressed with GABApi in these tumors was consistent with an immature cell type. In multivariate linear regression analysis, the level of GABApi gene expression was associated with ER-/HER2- phenotype (P < 0.0001), younger age at diagnosis (P = 0.0003), and shorter lifetime duration of breastfeeding (< or = 6 months) in all women (P = 0.017) and specifically in parous women (P = 0.013). GABApi gene expression was also associated with combinations of high grade with ER-/HER2- phenotype (P = 0.002), and with Hispanic ethnicity (P = 0.036). GABApi gene expression is increased in breast cancers of immature (undifferentiated) cell type and is significantly associated with shorter lifetime history of breastfeeding and with high-grade breast cancer in Hispanic women.

First analysis of patient demographics, technical reproducibility, cosmesis, and early toxicity: results of the American Society of Breast Surgeons MammoSite breast brachytherapy trial.

BACKGROUND: Eighty-seven institutions participated in a Registry Trial that was designed to collect data on the clinical use of the MammoSite breast brachytherapy catheter for delivering breast irradiation. Patient demographics, technical reproducibility, cosmesis, and early toxicity were evaluated. METHODS: From May 4, 2002 through July 30, 2004, 1419 patients with Stage 0, I, or II breast carcinoma who were undergoing breast-conserving therapy were enrolled on the trial. The device was placed in 1403 of these patients. The 1237 patients (87% of enrolled patients) who received accelerated partial breast irradiation (APBI) (34 grays prescribed to 1.0 cm in 10 fractions; 95% of patients who received APBI) constituted the study population; 86% of those patients (1068) had Stages I-II breast carcinoma (median tumor size, 10 mm), and 14% of those patients (169) had Stage 0 breast carcinoma. Ninety-one percent of the patients with invasive carcinoma (977 of 1068 patients) had negative lymph node status, and 99% of all patients had negative margins. The median patient age was 65 years. Systemic chemotherapy alone was administered to 79 patients with invasive carcinoma (7%), hormone therapy was administered to 501 patients (45%), and both were administered to 39 patients (4%). The median follow-up was 5 months. RESULTS: Five hundred fifty-four catheters (45%) were placed with an open cavity at the time of lumpectomy, and 683 catheters (55%) were placed with a closed cavity after lumpectomy. Skin spacing ranged from 2 mm to 75 mm (median, 10 mm). In 89% of patients, there was a minimum balloon-to-skin distance of 7 mm (2% of patients had distances < 5 mm). In terms of cosmetic assessment, 95% of patients (1030 of 1084 patients) who had a cosmetic assessment had a good/excellent result (last follow-up visit). Cosmetic results at 12 months were good/excellent in 92% of 248 evaluable patients. The median skin spacing (> or = 7 mm vs. < 7 mm) was associated significantly with a good/excellent cosmetic result (96.1% vs. 86.8%; P = 0.0001) overall and at 6 months (P = 0.006). Increasing skin spacing was associated with a good/excellent cosmetic result as a continuous variable (P < 0.0001). In total, 92 of 1140 evaluable patients (8.1%) developed an infection in the breast, which was device-related in 5.3% of patients (60 of 1140 patients). Good/excellent cosmetic results were noted in 86% of these patients (last follow-up visit). Fifteen of 442 evaluable patients (3.4%) developed a radiation recall reaction. Good/excellent cosmetic results were noted in 93% of these patients at their last follow-up visit. One local recurrence (0.1%) was reported (new primary carcinoma). CONCLUSIONS: Clinical evaluation of the ability of the MammoSite breast brachytherapy catheter to deliver APBI demonstrated acceptable technical reproducibility between multiple institutions and use in appropriate groups of patients. Cosmetic results at 12 months (92% good/excellent) were comparable to those reported with whole-breast RT. Early toxicity rates (infections, radiation recall) appeared to be acceptable.

Characterization of foam cells in nipple aspirate fluid.

Foam cells with abundant vacuolated cytoplasm are prominent in most samples of spontaneous nipple discharge, nipple aspirate fluid, and ductal lavage. Although several investigators have attempted to characterize these cells, there is no consensus about whether these cells are derived entirely from macrophages or from both ductal epithelial cells and macrophages. Using immunocytochemical methods, we studied 20 paired specimens of nipple aspirate fluid containing abundant foam cells obtained from the involved breast of women with in situ or invasive carcinoma and from the contralateral normal breast. We used a cocktail of anticytokeratin antibodies including AE1, AE3, and CAM5.2 and the macrophage marker KP1 (CD68). In addition, we examined samples by electron microscopy. The foam cells were consistently negative for cytokeratin and positive for CD68. In every case electron microscopy of these cells revealed irregular outlines with short cytoplasmic processes. The cytoplasm was abundant and contained numerous lysosomes, a small Golgi complex, lipid droplets, mitochondria, and short profiles of rough endoplasmic reticulum. There was no evidence, however, of cell junctions or tonofilaments. The immunocytochemical and electron microscopic findings of our study together clearly support a macrophage derivation for foam cells in nipple aspirate fluid.

Ductal lavage for detection of cellular atypia in women at high risk for breast cancer.

BACKGROUND: Breast cancer originates in breast epithelium and is associated with progressive molecular and morphologic changes. Women with atypical breast ductal epithelial cells have an increased relative risk of breast cancer. In this study, ductal lavage, a new procedure for collecting ductal cells with a microcatheter, was compared with nipple aspiration with regard to safety, tolerability, and the ability to detect abnormal breast epithelial cells. METHODS: Women at high risk for breast cancer who had nonsuspicious mammograms and clinical breast examinations underwent nipple aspiration followed by lavage of fluid-yielding ducts. All statistical tests were two-sided. RESULTS: The 507 women enrolled included 291 (57%) with a history of breast cancer and 199 (39%) with a 5-year Gail risk for breast cancer of 1.7% or more. Nipple aspirate fluid (NAF) samples were evaluated cytologically for 417 women, and ductal lavage samples were evaluated for 383 women. Adequate samples for diagnosis were collected from 111 (27%) and 299 (78%) women, respectively. A median of 13,500 epithelial cells per duct (range, 43-492,000 cells) was collected by ductal lavage compared with a median of 120 epithelial cells per breast (range, 10-74,300) collected by nipple aspiration. For ductal lavage, 92 (24%) subjects had abnormal cells that were mildly (17%) or markedly (6%) atypical or malignant (<1%). For NAF, corresponding percentages were 6%, 3%, and fewer than 1%. Ductal lavage detected abnormal intraductal breast cells 3.2 times more often than nipple aspiration (79 versus 25 breasts; McNemar's test, P<.001). No serious procedure-related adverse events were reported. CONCLUSIONS: Large numbers of ductal cells can be collected by ductal lavage to detect atypical cellular changes within the breast. Ductal lavage is a safe and well-tolerated procedure and is a more sensitive method of detecting cellular atypia than nipple aspiration.