Resection of Cavity Shave Margins in Stage 0-III Breast Cancer Patients Undergoing Breast Conserving Surgery: A Prospective Multicenter Randomized Controlled Trial.

OBJECTIVE: Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings. METHODS: In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0-III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM ("shave" group) or not ("no shave" group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates. RESULTS: Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the "shave" group and 200 to the "no shave" group. Median patient age was 65 years (range; 29-94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the "shave" and "no shave" groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the "shave" group were significantly less likely than those in the "no shave" group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001). CONCLUSION: Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM.

Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors.

PURPOSE: Discordance between HER2 expression in tumor tissue (tHER2) and HER2 status on circulating tumor cells (cHER2) has been reported. It remains largely underexplored whether patients with tHER2-/cHER2+ can benefit from anti-HER2 targeted therapies. METHODS: cHER2 status was determined in 105 advanced-stage patients with tHER2- breast tumors. Association between cHER2 status and progression-free survival (PFS) was analyzed by univariate and multivariate Cox models and survival differences were compared by Kaplan-Meier method. RESULTS: Compared to the patients with low-risk cHER2 (cHER2+ < 2), those with high-risk cHER2 (cHER2+ ≥ 2) had shorter survival time and an increased risk for disease progression (hazard ratio [HR] 2.16, 95% confidence interval [CI] 1.20-3.88, P = 0.010). Among the patients with high-risk cHER2, those who received anti-HER2 targeted therapies had improved PFS compared with those who did not (HR 0.30, 95% CI 0.10-0.92, P = 0.035). In comparison, anti-HER2 targeted therapy did not affect PFS among those with low-risk cHER2 (HR 0.70, 95% CI 0.36-1.38, P = 0.306). Similar results were obtained after adjusting covariates. A longitudinal analysis of 67 patients with cHER2 detected during follow-ups found that those whose cHER2 status changed from high-risk at baseline to low-risk at first follow-up exhibited a significantly improved survival compared to those whose cHER2 remained high-risk (median PFS: 11.7 weeks vs. 2.0 weeks, log-rank P = 0.001). CONCLUSION: In advanced-stage breast cancer patients with tHER2- tumors, cHER2 status has the potential to guide the use of anti-HER2 targeted therapy in patients with high-risk cHER2.

Nipple-sparing mastectomy: A review of outcomes at a single institution.

Nipple-sparing mastectomy (NSM) offers patients who are not candidates for breast-conserving treatment an aesthetically pleasing alternative to traditional mastectomy. Some studies have demonstrated its oncologic safety while others have demonstrated residual occult tumor cells at the nipple-areolar complex (NAC). These data prompt further review of oncologic outcomes after NSM.A single institution retrospective chart review was performed of all NSMs performed by 4 breast surgeons at Thomas Jefferson University Hospital over a span of 2012-2019. In this cohort, we review the reconstruction performed, axillary lymph node status, surgical margins, final pathology, loss of the NAC, recurrence rates, and follow-up. In our cohort, we reviewed 170 NSMs performed on 105 patients. All patients were female, and the average age was 46.9 years. Prophylactic procedures were performed on 43% of patients with 17.1% of patients being BRCA positive. Of those undergoing NSM for cancer (n = 94), the associated pathology was 28.8% DCIS, 32.9% IDC, and 3.5% ILC (this accounts for some patients with multiple diagnoses on final pathology). Sentinel lymph node biopsy (SLNB) was performed in 52.9% of cases with 10.6% of cases being positive for axillary disease. Margins were positive in 10.6% (n = 10) of cases performed for cancer with 8.5% (n = 8) of cases having positive margin at the NAC and the remainder being at the deep margin. Based on margin positivity, 2.4% (n = 4) of patients underwent redo surgery with 1 patient requiring re-resection at the NAC margin and 3 patients having total NAC resection. Total loss of NAC occurred in 5.9% (n = 10) of cases due to positive margins (n = 3) and necrosis (n = 7). Recurrence occurred in 7.2% (n = 7) of cases who underwent NSM for cancer. Locoregional recurrence in breast tissue, skin, or axilla occurred in 4.1% (n = 4) of cases with 0 recurrences at the NAC. Distant recurrence occurred in 4.1% (n = 4) of cases at both liver and bone. Average time to recurrence was 27.3 months. Of the 170 NSM performed, 98% had immediate tissue expander placement with 60% converting to permanent subpectoral implant reconstruction, 14% latissimus dorsi flap reconstruction, 0.6% delayed deep inferior epigastric artery perforator free-flap reconstruction, and 5.2% undergoing delayed free transversus abdominus muscle flap reconstruction. Of all the cases reviewed, there was only 1 death. Our average follow-up was 26.7 months. We demonstrate similar numbers in our analysis as other studies that have looked at oncologic outcomes after NSM. Although we demonstrate evidence of occult disease at the NAC margin when performing NSM, there was no evidence of recurrence at the NAC demonstrating its efficacy and safety. With proper patient selection, this procedure can be safely offered as an esthetically appealing alternative to traditional mastectomy.

Is radial scar on core needle biopsy a risk factor for malignancy? A single-center retrospective review and implications for management.

INTRODUCTION: Reported upgrade rate to malignancy of radial scars (RS) ranges widely (0%-40%) making management controversial. METHODS: A retrospective chart review was performed on patients with RS on core needle biopsy (CNB). Upgrade rates to malignancy and atypia on surgical excision were evaluated. RESULTS: Of 127 patients with RS on CNB, 53 were excluded due to malignancy or missing records. Of 74 patients reviewed, 52 (70.3%) had surgical excision with four (7.7%) upgraded to malignancy. Eight patients (10.8%) had atypia with RS on CNB with two (25%) upgraded to malignancy. When isolated RS was on CNB, 2 of 44 (4.5%) upgraded to malignancy while 15 of 44 (34%) had atypia on excision. Of 22 patients (29.7%) who did not have excision, zero developed cancer. CONCLUSION: We found higher than expected upgrade rates of isolated RS to atypia which can alter management. Additionally, 25% of RS with atypia upgraded to malignancy suggesting these patients are at higher risk.

A Randomized, Controlled Trial of Cavity Shave Margins in Breast Cancer.

BACKGROUND: Routine resection of cavity shave margins (additional tissue circumferentially around the cavity left by partial mastectomy) may reduce the rates of positive margins (margins positive for tumor) and reexcision among patients undergoing partial mastectomy for breast cancer. METHODS: In this randomized, controlled trial, we assigned, in a 1:1 ratio, 235 patients with breast cancer of stage 0 to III who were undergoing partial mastectomy, with or without resection of selective margins, to have further cavity shave margins resected (shave group) or not to have further cavity shave margins resected (no-shave group). Randomization occurred intraoperatively after surgeons had completed standard partial mastectomy. Positive margins were defined as tumor touching the edge of the specimen that was removed in the case of invasive cancer and tumor that was within 1 mm of the edge of the specimen removed in the case of ductal carcinoma in situ. The rate of positive margins was the primary outcome measure; secondary outcome measures included cosmesis and the volume of tissue resected. RESULTS: The median age of the patients was 61 years (range, 33 to 94). On final pathological testing, 54 patients (23%) had invasive cancer, 45 (19%) had ductal carcinoma in situ, and 125 (53%) had both; 11 patients had no further disease. The median size of the tumor in the greatest diameter was 1.1 cm (range, 0 to 6.5) in patients with invasive carcinoma and 1.0 cm (range, 0 to 9.3) in patients with ductal carcinoma in situ. Groups were well matched at baseline with respect to demographic and clinicopathological characteristics. The rate of positive margins after partial mastectomy (before randomization) was similar in the shave group and the no-shave group (36% and 34%, respectively; P=0.69). After randomization, patients in the shave group had a significantly lower rate of positive margins than did those in the no-shave group (19% vs. 34%, P=0.01), as well as a lower rate of second surgery for margin clearance (10% vs. 21%, P=0.02). There was no significant difference in complications between the two groups. CONCLUSIONS: Cavity shaving halved the rates of positive margins and reexcision among patients with partial mastectomy. (Funded by the Yale Cancer Center; ClinicalTrials.gov number, NCT01452399.).

Economic Impact of Routine Cavity Margins Versus Standard Partial Mastectomy in Breast Cancer Patients: Results of a Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to compare costs associated with excision of routine cavity shave margins (CSM) versus standard partial mastectomy (PM) in patients with breast cancer. BACKGROUND: Excision of CSM reduces re-excision rates by more than 50%. The economic implications of this is, however, unclear. METHODS: Between October 21, 2011 and November 25, 2013, 235 women undergoing PM for Stage 0-III breast cancer were randomized to undergo either standard PM ("no shave", n = 116) or have additional CSM taken ("shave", n = 119). Costs from both a payer and a hospital perspective were measured for index surgery and breast cancer surgery-related care through subsequent 90 days. RESULTS: The 2 groups were well-matched in terms of baseline characteristics. Those in the "shave" group had a longer operative time at the initial surgery (median 76 vs 66 min, P < 0.01), but a lower re-excision rate for positive margins (13/119 = 10.9% vs 32/116 = 27.6%, P < 0.01). Actual direct hospital costs associated with operating room time ($1315 vs. $1137, P = 0.03) and pathology costs ($1195 vs $795, P < 0.01) were greater for the initial surgery in patients in the "shave" group. Taking into account the index surgery and the subsequent 90 days, there was no significant difference in cost from either the payer ($10,476 vs $11,219, P = 0.40) or hospital perspective ($5090 vs $5116, P = 0.37) between the "shave" and "no shave" groups. CONCLUSIONS: Overall costs were not significantly different between the "shave" and "no shave" groups due to significantly fewer reoperative surgeries in the former.

Intraductal Papilloma with Benign Pathology on Breast Core Biopsy: To Excise or Not?

BACKGROUND: The management of intraductal papillomas on core biopsy continues to be controversial. Papillomas with atypia are typically excised. However, it is unclear whether surgical excision is warranted for benign lesions. METHODS: A retrospective review of our institution's pathology and radiology databases from January 2009 through May 2014 identified 119 patients with a diagnosis of benign papilloma without atypia on core biopsy. We determined the rate of carcinoma identification on surgical excision. RESULTS: The average patient age was 52.8 years (range 24-84 years). Indication for core biopsy included: abnormal imaging (n = 106), nipple discharge (n = 21), or palpable mass (n = 24). Seventy-five patients underwent surgical excision after core biopsy. Sixteen patients (21.3 %) had atypia in the excision specimen (combination atypical ductal hyperplasia, n = 11; atypical lobular hyperplasia, n = 8; lobular carcinoma-in situ, n = 3), 15 (93.8 %) of which were in the surrounding breast tissue. Two patients (2.7 %) had malignancy (ductal carcinoma-in situ and micropapillary carcinoma-in situ). As a result of surgical findings, 12 % of patients had a change in management. In comparing those with benign findings on surgical pathology and those whose disease was upstaged, there was no statistically significant difference in family history of breast cancer, indication for core biopsy, mammographic findings, or location of papilloma. CONCLUSIONS: Benign papillomas diagnosed on core biopsy are rarely upstaged to malignancy on surgical excision. However, at least 21 % of patients may have atypical findings in the surrounding tissue, which could change clinical management. Surgical excision should be considered in patients with benign papillomas.

Frozen section evaluation of breast carcinoma sentinel lymph nodes: a retrospective review of 1,940 cases.

Many sentinel lymph node biopsies (SLNBs) are evaluated intraoperatively by frozen section, which may impact the need for further axillary dissection (AD). However, the need for AD in patients with small metastases has been recently called into question, meaning that frozen SLNB may be unnecessary. Furthermore, frozen section can compromise tissue for further study. At our institution, we grossly evaluate all SLNB and freeze half of the node. Here, we evaluate the frozen SLNB discrepancy rate using this method, focusing on cause of discrepancy and need for further surgery. We reviewed surgical pathology records for all breast cancer resections with frozen section of SLNB examined from 2003 to 2012. For cases with a frozen section discrepancy, we compiled clinicopathologic data. In total, 1,940 cases involved frozen section evaluation of SLNB. In 95 cases (4.9% of total cases, 23.8% of positive node cases), the SLNB was called negative on frozen but positive on final examination (false negatives). The majority of missed metastases are isolated tumor cells or micrometastases. A trend was observed toward fewer patients receiving completion AD after a discrepant frozen SLNB in the later years of the study. The protocol of freezing half of a SLNB is a reasonable method, with results similar to or better than other studies. The main adverse outcome is the need for separate AD; however, additional positive nodes are uncommon. The trend of fewer patients getting additional AD after a discrepant frozen SLNB suggests that clinicians may be using this information differently recently.

The number of lymph nodes dissected in breast cancer patients influences the accuracy of prognosis.

BACKGROUND: Recent trials have suggested that axillary node dissection may not be warranted in some breast cancer patients with one to two positive nodes. Given that lymph node ratio (LNR; number of positive lymph nodes divided by the total examined) has been shown to be a significant prognostic factor, we sought to determine whether the number of nodes removed in this low risk population predicted survival. METHODS: The National Cancer Database is a comprehensive clinical surveillance resource capturing 70% of newly diagnosed malignancies in the United States; 309,216 breast cancer patients diagnosed between 1998 and 2005, with tumors ≤5 cm and one to two positive nodes, formed the cohort of interest. RESULTS: Median age at diagnosis was 57 (range 18-90) years. Median tumor size was 2 (range 0.1-5) cm; 215,382 patients (69.7%) had one positive node, and 93,834 (30.3%) had two. The median number of lymph nodes examined was 11 (range 1-84). Patients were categorized into low (≤0.2), medium (0.21-0.65), or high (>0.65) LNR groups, with 228,822 (74%), 55,797 (18%), and 24,597 (8%) patients in each of these categories, respectively. Median follow-up was 54.1 months. Median overall survival (OS) for low, intermediate, and high LNR was 66.1, 61.1, and 56.5 months, respectively (p < 0.001). In a Cox model controlling for clinicopathologic and therapy covariates, LNR category remained a significant predictor of OS (p < 0.001). CONCLUSIONS: LNR is an independent predictor of OS in a low-risk population with one to two positive nodes and tumors ≤5 cm. Therefore, the number of lymph nodes excised may influence prognostic stratification.

Is there a correlation between breast cancer molecular subtype using receptors as surrogates and mammographic appearance?

BACKGROUND: The identification of distinct molecular subtypes has changed breast cancer management. The correlation between mammographic appearance and molecular subtype for invasive breast cancer has not been extensively studied. METHODS: A retrospective review of our prospectively collected database was performed to evaluate the mammographic appearance and molecular subtypes of all cases of invasive breast cancers diagnosed between 2003 and 2010. RESULTS: There were 985 cases of invasive breast cancer with complete data on receptor status and mammographic appearance. The most common mammographic finding was a mass (61 %), and the most common molecular subtype was ER/PR positive, HER2 negative (71 %). On univariate analysis, race, stage, and histology were all significantly associated with molecular subtype. On multivariate analysis, the luminal molecular type was associated with architectural distortion [odds ratio (OR) 4.3, 95 % CI 1.3-14.1]; HER2 positive cancers, either with or without ER/PR expression, were more likely to be associated with mammographic calcifications (OR 2.8 and 3.1, respectively; 95 % CI 1.7-4.8 and 1.7-5.5); and triple negative cancers were most likely to be associated with a mammographic mass (OR 2.5; 95 % CI 1.4-4.4). CONCLUSIONS: We observed several characteristic associations between molecular subtype and mammographic appearance. Improved understanding of these associations may help guide clinical decision making and provide information about underlying tumor biology.

Impact of Cavity Shave Margins on Margin Status in Patients with Pure Ductal Carcinoma In Situ.

BACKGROUND: We examined the impact of cavity shave margins (CSMs) on margin status in patients with pure ductal carcinoma in situ (DCIS) undergoing partial mastectomy (PM). METHODS: One hundred and nine patients from 2 multicenter, randomized controlled trials were identified with pure DCIS (no invasive cancer). Surgeons performed their best PM, with specimen radiography and resection of selective margins per surgeon discretion. Patients were then randomized to have CSM resected or not. A positive margin was defined as <2 mm from ink. RESULTS: Median patient age was 63 years; median size of DCIS was 1.20 cm; 43.6% of patients had high-grade DCIS; and 58 (53.2%) patients were randomized to take CSM. The "shave" and "no-shave" groups were well-matched for age, race, ethnicity, palpability, grade, and size of DCIS. Although 33 (56.9%) of the patients in the shave group had a positive margin before randomization, only 12 (20.7%) had a positive margin after randomization to CSM (p < 0.001). In the no-shave group, 17 patients (33.3%) had a positive margin. Controlling for size and grade of DCIS, taking CSM resulted in a nearly 65% reduction in the positive-margin rate (odds ratio 0.366; 95% CI, 0.136 to 0.981; p = 0.046). Size of DCIS remained an independent predictor of positive margins in the model (odds ratio 1.646; 95% CI, 1.227 to 2.209; p = 0.001). CONCLUSIONS: CSM reduces positive-margin rates in patients with pure DCIS, and can be a practical solution for DCIS patients who tend to have a high rate of margin positivity.

A unique proteolytic fragment of alpha1-antitrypsin is elevated in ductal fluid of breast cancer patient.

By comparison of mass spectra from a small cohort of nipple aspiration fluids (NAF), we previously discovered a panel of five candidate breast cancer biomarkers among them an unidentified 4.7 kD peptide BF5. The purposes of the present study were to verify the presence of BF5 in an independent cohort; to determine the protein identity of BF5; and to provide insight into the biology of BF5 production and elevation in tumor-associated NAF. We prospectively collected bilaterally matched NAF from patients with unilateral Stage I/II breast cancer (IBC-31), ductal carcinoma in situ (DCIS-6), atypical ductal hyperplasia (ADH-5), and presumed healthy women who came to routine mammography and had a normal exam (31). Following the consolidation of its cancer-associated expression on SELDI-mass spectrometry, BF5 was isolated by gel electrophoresis and sequenced by tandem mass spectrometry. BF5 was elevated in 15-25% of women with IBC, DCIS, or ADH vs. 0% of controls. This elevation was restricted to the affected breasts. BF5 was identified as 41/42-aa C-terminal peptide of alpha1-antitrypsin (AAT), the principle inhibitor of serine protease neutrophile elastase. The full length AAT showed a consistent expression pattern as C-41/42, and C-41/42 can be generated in vitro by MMP-7 cleavage. In conclusion, elevated C-41/42 is likely the result of elevated AAT synthesis, and the activity of specific MMPs present within the tumor. As other C-terminal fragments of AAT are reported to function as tumor-derived suppressors to the host immune-system, elevated C-41/42 may also be predictive of a poor outcome.

Association of clinical outcomes in metastatic breast cancer patients with circulating tumour cell and circulating cell-free DNA.

BACKGROUND: Both circulating tumour cell (CTC) and total circulating cell-free DNA (ccfDNA) predict cancer patient prognosis. However, no study has explored the prognostic value of the combined use of CTC and ccfDNA. We aimed to investigate individual and joint effects of CTC and ccfDNA on clinical outcomes of metastatic breast cancer (MBC) patients. METHODS: We collected 227 blood samples from 117 MBC patients. CTCs were enumerated using the CellSearch System. ccfDNAs were quantified by quantitative real-time polymerase chain reaction and Qubit fluorometer. The individual and joint effects of CTC and ccfDNA levels on patient progression-free survival (PFS) and overall survival (OS) were analysed using Cox proportional hazards models. RESULTS: Compared to patients with <5 CTCs, patients with ≥5 CTCs had a 2.58-fold increased risk of progression and 3.63-fold increased risk of death. High level of ccfDNA was associated with a 2.05-fold increased risk of progression and 3.56-fold increased risk of death. These associations remained significant after adjusting for other important clinical covariates and CTC/ccfDNA levels. CTC and ccfDNA levels had a joint effect on patient outcomes. Compared to patients with low levels of both CTC and ccfDNA, those with high levels of both markers exhibited a >17-fold increased death risk (P < 0.001). Moreover, longitudinal analysis of 132 samples from 22 patients suggested that the inconsistency between CTC level and outcome in some patients could possibly be explained by ccfDNA level. CONCLUSIONS: CTC and total ccfDNA levels were individually and jointly associated with PFS and OS in MBC patients.

The superficial margin of the skin-sparing mastectomy for breast carcinoma: factors predicting involvement and efficacy of additional margin sampling.

BACKGROUND: No study has systematically evaluated the significance of involvement of the superficial specimen margin in skin-sparing mastectomies (SSMs). METHODS: 168 SSMs with a small, additional superficial margin (ASM) specimen taken directly over the tumor to the dermis intraoperatively were studied. RESULTS: 64 SSMs (38%) had a positive superficial specimen margin but only 13 (20%) of these had residual breast carcinoma in ASMs. Only 1 of 104 SSMs with a negative superficial specimen margin had residual breast carcinoma in its ASM (P < 0.05). ASM sampling rendered the final true margin directly over the tumor negative in 54 of 58 (93%) SSMs with a focally positive superficial specimen margin, but did not negate the nonfocally positive superficial specimen margin in six other cases. In SSMs with a positive superficial specimen margin, multivariate analysis revealed that the presence of extensive ductal carcinoma in situ (DCIS) in the SSM and a thicker ASM specimen were the only independent factors predictive of residual breast carcinoma in ASM. Eighty-nine (53%) ASMs contained benign breast tissue. CONCLUSIONS: Superficial specimen margins in SSMs are often microscopically positive and approximately half of ASMs contain benign breast tissue, likely reflecting the difficulty in completely removing breast tissue near the skin flaps in SSMs. ASM sampling effectively decreases positive superficial specimen margins directly over the tumor in SSMs, but fails to account for positive superficial specimen margins in other quadrants in patients with multicentric disease, especially extensive DCIS. Patients whose superficial margins remain positive could potentially represent a subset of patients for whom postmastectomy radiation is beneficial.

Nipple-sparing mastectomy: critical assessment of 51 procedures and implications for selection criteria.

BACKGROUND: Retrospective studies have shown that occult nipple-areolar complex (NAC) involvement in breast cancer is low, occurring in 6-10% of women undergoing skin-sparing mastectomy (SSM). The cosmetic result and high patient satisfaction of nipple-sparing mastectomy (NSM) has prompted further evaluation of the oncologic safety of this procedure. METHODS: We conducted a retrospective chart review of 36 self-selected patients who underwent 51 NSM procedures between 2002 and 2007. Criterion for patient selection was no clinical evidence of nipple-areolar tumor involvement. All patients had the base of the NAC evaluated for occult tumor by permanent histologic section assessment. We also evaluated tumor size, location, axillary node status, recurrence rate, and cosmetic result. RESULTS: Malignant NAC involvement was found in 2 of 34 NSM (5.9%) completed for cancer which prompted subsequent removal of the NAC. Of the 51 NSM, 17 were for prophylaxis, 10 for ductal carcinoma in situ (DCIS), and 24 for invasive cancer. The average tumor size was 2.8 cm for invasive cancer and 2.5 cm for DCIS. Nine patients had positive axillary nodes. Overall, 94% of the tumors were located peripherally in the breast. After mean follow-up of 18 months, only two patients (5.9%) had local recurrence. CONCLUSION: Using careful patient selection and careful pathological evaluation of the subareolar breast tissue at surgery, NSM can be an oncologically safe procedure in patients where this is important to their quality of life. A prospective study based on focused selection criteria and long-term follow-up is currently in progress.

The role of ultrasound-guided fine-needle aspiration of axillary nodes in the staging of breast cancer.

BACKGROUND: As a complement to sentinel node dissection (SLND), we evaluated ultrasound-guided fine-needle aspiration (USFNA) of normal and abnormal axillary nodes in breast cancer patients. We hypothesized that USFNA would be accurate for primary breast tumors larger than 2 cm. METHODS: We retrospectively reviewed 68 patients who underwent 69 preoperative USFNAs from 2003 to 2005. The results of 65 preoperative USFNA were compared with the results of SLND or axillary node dissection (ALND) for concordance. Four USFNAs were excluded from analysis because of a complete response to neoadjuvant therapy. We evaluated whether primary tumor features (histology, size, grade, vascular invasion, estrogen/progesterone receptor status and Her-2-neu status) predicted concordance of USFNA results and the final lymph node pathology. RESULTS: Of 65 axillae analyzed, 39 (60%) were positive, four (6%) were non-diagnostic, and 22 (34%) were negative by USFNA. USFNA had 89% sensitivity, 100% specificity, and 100% positive predictive value (PPV) in patients with palpable or ultrasonographically suspicious nodes. USFNA sensitivity dropped significantly for nonpalpable, ultrasonographically normal nodes (54%), while specificity and PPV remained 100%. None of the primary tumor features predicted concordance of USFNA and SLND/ALND. CONCLUSIONS: USFNA of axillary nodes has a high specificity and PPV in clinically or radiologically suspicious nodes. Sensitivity of USFNA is low for nodes of normal appearance, but positive USFNA may allow definitive management of the axilla without a SLND. Thus, USFNA of normal appearing nodes might be beneficial in cases where decisions regarding neoadjuvant chemotherapy would be affected by the results.

The role of breast MRI in the management of patients with breast disease.

Breast MRI has paved the way for new thinking regarding the workup of women recently diagnosed with breast cancer and the screening of high-risk women. The routine use of MRI preoperatively is advocated, particularly in young patients and women with dense breasts where mammography is significantly less sensitive for the detection of malignancy. Additionally, MRI is particularly helpful in those women who have core biopsy results showing extensive intraductal component (>25%) orinvasive lobular carcinoma, and in those women with increased risk of positive margins. However, as with any imaging modality, breast magnetic resonance has limitations. Because breast magnetic resonance has lower specificity than some modalities, clinicians must be selective in identifying those women most likely to benefit from this additional imaging. Many recent publications show that MRI does not unduly raise the false-positive biopsy rate while providing specificity similar to that of mammography and higher than that of ultrasound. Positive margin rates for breast conservation therapy range from 30% to 50% and the achievement of negative margins is directly related to low recurrence rates. Magnetic resonance provides improved preoperative staging, which in turn may reduce recurrence rates and improve patient outcome. Breast MRI should be used in concert with other modalities, such as mammography and ultrasound, for the highest sensitivity for detecting malignancy. Long-term studies are needed to validate the impact of screening and diagnostic breast MRI on patient outcomes.

Do All Positive Margins in Breast Cancer Patients Undergoing a Partial Mastectomy Need to Be Resected?

BACKGROUND: Positive margins have been reported in 20% to 40% of patients undergoing a partial mastectomy, often resulting in re-excision. How often the re-excision yields additional cancer and whether there are predictors of residual disease remain unknown. STUDY DESIGN: Patients who had a positive margin (defined as tumor at ink for patients with invasive disease or within 1 mm for patients with ductal carcinoma in situ) in the SHAVE (A Randomized Controlled Trial of Routine Shave Margins Versus Standard Partial Mastectomy in Breast Cancer Patients) trial before randomization were evaluated to determine the rate of additional disease either in cavity shave margins or at re-excision. Details of the SHAVE trial can be found elsewhere. RESULTS: Of the 235 patients in the trial, 82 (34.9%) had a positive margin before randomization; 58 of these patients underwent either cavity shave margins excision or a re-excision of the positive margin(s). Twenty-one (36.2%) patients had residual disease. On bivariate analysis, residual disease was associated with younger patient age (median 51 vs 62 years; p = 0.007), and the presence of high-grade ductal carcinoma in situ (57.1% vs 31.3% for grade 2 and 0% for grade 1; p = 0.025). The following factors were not associated with further disease: patient race; ethnicity; BMI; volume of resection; number of positive margins; extent of ductal carcinoma in situ; and extent, grade, and histologic subtype of invasive cancer. On multivariate analysis, only patient age younger than 60 years remained a significant predictor of residual disease (odds ratio 3.920; 95% CI 1.081 to 14.220; p = 0.038). CONCLUSIONS: Positive margins are associated with further disease in more than one-third of patients and, aside from young age, there are no predictors of this. These findings support continued re-excision of positive margins, particularly in patients younger than 60 years of age.

Quality-of-Life Outcomes Improve with Nipple-Sparing Mastectomy and Breast Reconstruction.

BACKGROUND: Loss of the nipple-areola complex can be psychologically and sexually devastating. Nipple-sparing mastectomy provides robust cosmetic results, but few studies have investigated the quality-of-life outcomes associated with it. METHODS: The authors performed an institutional review board-approved retrospective study of 32 patients who underwent nipple-sparing mastectomy with implant-based or autologous reconstruction and 32 control patients who underwent non-nipple-sparing mastectomy with reconstruction matched by reconstruction type and operative period. They then compared premastectomy and postreconstruction responses to the BREAST-Q, a validated and breast reconstruction-specific quality-of-life questionnaire, within and between their study and control populations. RESULTS: The nipple-sparing and non-nipple-sparing mastectomy groups were statistically similar in terms of mean age [49.9 ± 8.5 years (range, 36 to 69 years) and 47.7 ± 10.3 years (range, 26 to 68 years) (p = 0.29), respectively] and mean body mass index [24.3 ± 3.5 kg/m (range, 17.9 to 33.7 kg/m) and 25.5 ± 5.4 kg/m (range, 19.2 to 39.2 kg/m) (p = 0.29), respectively]. There were no significant between-group differences in occurrence of postreconstruction complications. The authors found significantly higher mean postreconstruction scores in the nipple-sparing mastectomy group within the Satisfaction with Breasts (p = 0.039) and the Satisfaction with Outcome (p = 0.017) domains. Finally, they noted higher median postreconstruction scores in the nipple-sparing mastectomy group within the Psychosocial Well-being (p = 0.043) and Satisfaction with Breasts (p = 0.004) domains. CONCLUSIONS: Psychological concerns regarding malignancy may negatively impact premastectomy patient quality of life. Reconstructive surgery improves patients' postmastectomy quality of life. Nipple-sparing mastectomy appears to provide significantly better improvement in postreconstruction quality of life, specifically in the Satisfaction with Breasts and Satisfaction with Outcome domains of the BREAST-Q, compared with non-nipple-sparing mastectomies. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.