A comparison of clinical and pathologic assessments for the prediction of occult nipple involvement in nipple-sparing mastectomies.

BACKGROUND: Nipple-sparing mastectomy (NSM) for both risk reduction and cancer is increasing. In the cancer setting, most studies suggest the use of both clinical and intraoperative biopsy criteria in patient selection. This study examines the use of both biopsy and clinical criteria in women undergoing total nipple-removing mastectomy. METHODS: The study consisted of 58 patients undergoing total mastectomy without nipple sparing. Biopsies of the subareola tissue (SA), proximal nipple (NC) contents and radial sections of the residual nipple (NR) were examined microscopically. Tumor size and distance from the nipple were also noted. RESULTS: Using clinical criteria alone, the false negative rate was 53.8% and a false positive rate of 44.4%. When adding subareola and nipple core biopsies to clinical criteria the false negative rate fell to 7.7% but the false positive rate remained at 44.4%. When using only SA and NC biopsies to predict occult nipple involvement, the false negative rate was 11.8%. In 4 cases the NC was positive while the SA was negative for cancer and in 6 cases the SA was positive and NC negative. In 2 cases both the NC and SA biopsies were negative while the NR was positive. CONCLUSIONS: This study supports a more limited role in the use of clinical criteria for evaluating patients for NSM. This maximizes the number of patients who are candidates for NSM with minimal risk of nipple involvement. It was also noted that intraoperative biopsies are not totally reliable in predicting occult nipple involvement.

Reducing the risk of nipple necrosis: technical observations in 340 nipple-sparing mastectomies.

Optimizing cosmesis is a common goal of breast surgery. In support of immediate breast reconstruction, nipple-sparing techniques have evolved. There is still a lack of agreement on the optimal technique and skin flap necrosis can be problematic. In this study, we review our experience with 340 NSM. Between March 2006 and February 2011, 340 NSMs were performed. Mammography, ultrasonography and magnetic resonance imaging were reviewed. Patient demographics and surgical techniques were reviewed. Anatomic observations were made and supported by breast images. A total of 340 NSMs in 231 patients by a single surgeon (AJS) were reviewed. Risk reduction was the indication for surgery in 59% with 50 patients (21.6%) testing positive for a BRCA1/2 gene mutation. There were two flap losses and 14 hematomas. Complete nipple necrosis occurred in three cases (0.8%) and partial loss in six patients. Recommendations are made to reduce the risk of nipple necrosis included the following: (a) preserving major perforating vessels (b) elevating skin flaps in the plane between the subcutaneous fat and the breast glandular tissue (c) the use of incisions that do not devascularize the nipple-areola complex. Nipple-sparing mastectomy can be performed with an acceptably low risk of nipple necrosis. Attention to detail including preserving major perforating vessels, elevating skin flaps in the appropriate plane and careful attention to incision planning are all required for a consistently good cosmetic outcome.

Nipple-sparing mastectomy and immediate free-flap reconstruction in the large ptotic breast.

Because of increased risk for nipple necrosis, many surgeons believe large ptotic breasts to be a relative contraindication to nipple-sparing mastectomy (NSM). A retrospective review was performed on 85 consecutive patients who underwent NSM with 141 immediate perforator free-flap breast reconstructions. We analyzed the subset of patients with large ptotic breasts, defined as cup size C or greater, sternal notch to nipple distance greater than 24 cm and grade 2 or 3 breast ptosis. Of the 85 patients, 19 fit the inclusion criteria. Breast cup size ranged from 34C to 38DDD. There was 1 case of nipple necrosis in the patient with previous breast radiation (5%), 1 hematoma (5%), and no flap losses. Five (26%) patients underwent subsequent mastopexy or breast reduction, a mean of 6.6 months after the primary procedure. We demonstrate that NSM and free-flap breast reconstruction can be safely and reliably performed in selected patients.

Breast MRI: patterns of utilization and impact on patient management in the community hospital setting.

OBJECTIVE: The objective of our study was to investigate the indications for breast magnetic resonance imaging, or MRI, in our community hospital, determine how many probably benign MRI findings were malignant at follow-up, determine how many cancers were identified by MRI in screening patients, and evaluate the utility of MRI for surgical planning and problem-solving. MATERIALS AND METHODS: Five hundred twenty-eight contrast-enhanced MRI's of the breast in 434 patients were retrospectively reviewed. MRI images/reports were compared to surgical pathology reports and the results of follow-up studies. RESULTS: Screening was the most common indication for breast MRI in our patient population. Five percent of findings termed "probably benign" on MRI proved to be malignant at follow-up. Eight malignancies were detected in six of 202 screened patients. Ten malignancies were diagnosed in 66 patients referred to MRI for problem-solving. In two of 74 patients with known breast cancer, an unsuspected ipsilateral cancer was identified on MRI. CONCLUSION: MRI proved useful in the community hospital setting for screening high-risk patients and problem-solving. The rate of malignancy in probably benign MRI findings was higher than the corresponding rate in mammography. The detection of additional ipsilateral and contralateral cancers in pre-operative patients with known breast cancer was not as high as expected, based on prior studies.

Terminal duct lobular units are scarce in the nipple: implications for prophylactic nipple-sparing mastectomy: terminal duct lobular units in the nipple.

BACKGROUND: The use of nipple-sparing mastectomy (NSM) for both breast cancer treatment and risk reduction is increasing. There is no randomized data comparing nipple-sparing mastectomy with standard mastectomy techniques. There is evidence to suggest that ductal and lobular breast cancer arises in the terminal duct/lobular unit (TDLU). This study was undertaken to determine whether TDLUs exist in the nipple and if so, to what extent. METHODS: At the time of mastectomy the nipple papilla was excised and submitted for separate pathological examination. The presence or absence of TDLUs was noted. RESULTS: Thirty-two nipples were studied in 22 patients. There were no TDLUs in 29 specimens. Three of 32 nipple specimens were found to contain TDLUs. The three nipples contain one, two, and three TDLUs respectively. All TDLUs were found at the base of the nipple, with none located near the tip. CONCLUSIONS: The infrequent occurrence of TDLUs in the nipple papilla supports the use of NSM for risk reduction surgery, including for those women with BRCA1/2 mutations.

Technical considerations in nipple-sparing mastectomy: 82 consecutive cases without necrosis.

BACKGROUND: Even without comparative trials, nipple-sparing mastectomy (NSM) is gaining traction in the treatment of established breast cancer and in the prophylactic setting. As yet, there are no established techniques that are universally applied to NSM. Herein we describe our surgical approach. METHODS: All mastectomies performed by a single surgeon (AJS). Reconstructions performed included synthetic implants, deep inferior epigastric (DIEP) and gluteal artery perforator flaps (GAP). A lateral incision (12.1%) and a 6:00 radial incision (87.9%) were used in all patients. The areola was elevated just beneath the deep dermis and ductal tissue within the nipple papilla was "cored". RESULTS: Fifty-eight patients underwent 82 NSMs for both cancer and prophylaxis. No patient developed necrosis of the nipple-areola complex (NAC). Minor skin-edge necrosis not involving the NAC occurred in 2 patients. Four patients developed a hematoma, 2 requiring re-operation. One patient required re-operation to correct a vein problem. There were no flap losses. CONCLUSIONS: NSM can be performed with a minimal incidence of skin-flap related complications. In our hands, radial incisions perform well in this regard. Indications for NSM and the optimal technique are yet to be determined.

Descriptions and outcomes of insertion techniques of a breast brachytherapy balloon catheter in 1403 patients enrolled in the American Society of Breast Surgeons MammoSite breast brachytherapy registry trial.

BACKGROUND: The use of the MammoSite brachytherapy balloon catheter is 1 option for the delivery of accelerated partial breast irradiation during breast cancer therapy. The device can be inserted into the breast using 3 different techniques. This report describes these methods of insertion and correlates the technique with outcome data collected in a multi-institutional registry trial. METHODS: In the registry trial, MammoSite catheters were inserted either (1) at the time of lumpectomy into an open cavity, (2) after surgery with ultrasound guidance through a separate small lateral incision into a closed cavity, or (3) after surgery by entering directly through the lumpectomy wound (the scar entry technique). Device placement techniques in 1403 patients with early stage breast cancer treated at 87 institutions by 223 different investigators were documented in the registry. Data collected included number of cases of each technique, age of patient, tumor size, skin spacing, catheter pull rates and reasons, infection, radiation recall, cosmesis, and recurrence. RESULTS: Catheter placement at the time of lumpectomy was performed in 619 patients (44%), after surgery with ultrasound guidance in 576 patients (41%), and the scar entry technique technique in 197 patients (14%). The type of technique was not associated with age of patient, tumor size, bra size, catheter size, skin spacing, infection, radiation recall, cosmesis, or recurrence. There was a statistically significant increased incidence of premature catheter removals for pathologically related reasons with the open-cavity technique compared with the 2 postoperative methods secondary to final histology reports disqualifying the patient after MammoSite placement. CONCLUSIONS: These registry data show that the MammoSite catheter can be inserted with any 1 of 3 different techniques. A postoperative placement, after the final pathology report is issued, decreases the incidence of premature removal of the catheter because of disqualifying pathology.

Newly diagnosed breast cancer patients choose bilateral mastectomy over breast-conserving surgery when testing positive for a BRCA1/2 mutation.

In women diagnosed with breast cancer and testing positive for a BRCA1/2 mutation, decisions as to whether to undergo prophylactic risk-reduction surgery may differ from those women who test positive in a presymptomatic phase. Eighty-four women were identified who had undergone genetic testing at the time of breast cancer diagnosis. The study group consisted of 46 of these women who had initially undergone breast-conserving surgery. Eight patients (17.4%) tested positive for a mutation. Seven of the eight underwent bilateral prophylactic mastectomy prior to receiving radiation therapy. The only patient not undergoing bilateral mastectomy was awaiting liver transplant. Women who are candidates for breast-conserving surgery and who test positive for a breast cancer gene mutation choose mastectomy over surveillance.

Nipple-Sparing Mastectomy and Ptosis: Perforator Flap Breast Reconstruction Allows Full Secondary Mastopexy with Complete Nipple Areolar Repositioning.

BACKGROUND: Patients with moderate to severe ptosis are often considered poor candidates for nipple-sparing mastectomy. This results from the perceived risk of nipple necrosis and/or the inability of the reconstructive surgeon to reliably and effectively reposition the nipple-areola complex on the breast mound after mastectomy. METHODS: A retrospective review identified patients with grade II/III ptosis who underwent nipple-sparing mastectomy with immediate perforator flap reconstruction and subsequently underwent a mastopexy procedure. The mastopexies included complete, full-thickness periareolar incisions with peripheral undermining around the nipple-areola complex to allow for full transposition of the nipple-areola complex relative to the surrounding skin envelope. RESULTS: Seventy patients with 116 nipple-sparing mastectomies met inclusion criteria. The most common complications were minor incisional dehiscence (7.7 percent) and variable degrees of necrosis in the preserved breast skin (3.4 percent) after the initial mastectomy. There were no cases of nipple-areola complex necrosis following the secondary mastopexy. CONCLUSIONS: The authors demonstrate that full mastopexy, including a complete full-thickness periareolar incision and nipple-areola complex repositioning on the breast mound, can be safely performed after nipple-sparing mastectomy and perforator flap breast reconstruction. The underlying flap provides adequate vascular ingrowth to support the perfusion of the nipple-areola complex despite complete incisional interruption of the surrounding cutaneous blood supply. These findings may allow for inclusion of women with moderate to severe ptosis in the candidate pool for nipple-sparing mastectomy if oncologic criteria are otherwise met. These findings also represent a significant potential advantage of autogenous reconstruction over implant reconstruction in women with breast ptosis who desire nipple-sparing mastectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A comparison of methylene blue and lymphazurin in breast cancer sentinel node mapping.

BACKGROUND: When lymphazurin became unavailable to our institution, we elected to employ methylene blue to perform sentinel node mapping for patients with breast cancer. The purpose of this study was to compare methylene blue and lymphazurin for performing sentinel node mapping for breast cancer. METHODS: We evaluated our sentinel node mapping experience from April 1, 2001 to March 31, 2002. Patients were divided into two groups based on the dye used for lymphatic mapping. The two groups were compared to evaluate the results of the sentinel node mapping procedure. RESULTS: During the study period a total of 199 patients were evaluated with sentinel node mapping, 87 with lymphazurin and 112 with methylene blue. The two groups were similar in demonstrating the success of the sentinel node procedure, nodes identified per case, and technique used for node identification (colloid or dye, or both). CONCLUSIONS: In our initial experience, methylene blue appears to be equivalent to lymphazurin for sentinel node mapping in breast cancer.

Postmastectomy radiation in patients with four or more positive nodes.

Postmastectomy radiotherapy (PMR), a local therapeutic modality, is recommended to treat breast cancer patients with multiple involved axillary lymph nodes (a marker of increased systemic risk). Bothered by this conceptually flawed treatment approach we evaluated the impact of PMR on the treatment of women with four or more involved axillary lymph nodes. We identified 1164 patients treated from 1982 through 1999 with mastectomy. We reviewed the records of the 223 who demonstrated four or more positive axillary lymph nodes. Of these 128 were treated by mastectomy only and 95 by PMR. The mastectomy-only group demonstrated a mean tumor size of 3.5 cm, a median of seven axillary nodes involved, and a median of 24.9 nodes harvested. The PMR group had a mean tumor size of 4.3 cm with nine positive nodes out of a median total of 23.3 harvested. The difference in mean tumor size was statistically significant (P = 0.01). The locoregional recurrence (10.9% vs 12.6%), distant recurrence rates (42.2% vs 35.8%), and 5-year survival (51% vs 55%) were not statistically different between the mastectomy-only group versus the PMR group, respectively. Adding PMR to breast cancer treatment demonstrated no improvement in outcome. Despite limitations of this retrospective study the results strongly support evaluation of PMR by a high-quality randomized prospective trial.

The evolution in management of patients with subcentimeter, node-negative, triple-negative breast cancer.

BACKGROUND: The aim of this study was to determine the evolution in treatment recommendations and outcomes for patients with subcentimeter, node-negative, triple-negative disease. METHODS: Patients were divided into a remote (diagnosed from 1997 to 2003) and a recent (diagnosed from 2004 to 2011) group. Demographics, tumor size, surgical treatment, use of adjuvant chemotherapy, survival, and disease recurrence were evaluated. RESULTS: Thirty patients were placed in the remote group and 31 in the recent group. Demographics, tumor sizes, and surgical treatment were similar between groups. The use of adjuvant chemotherapy increased from 7% to 42% in the recent group (P < .002). Disease-free survival and recurrence (7%) was not influenced by the use of chemotherapy. CONCLUSIONS: This study demonstrates that adjuvant chemotherapy is increasingly used in patients with the triple-negative phenotype, regardless of other favorable prognostic variables. The value of adjuvant chemotherapy for the subgroup of patients in our study is unclear and mandates further investigation.

Buried flap reconstruction after nipple-sparing mastectomy: advancing toward single-stage breast reconstruction.

BACKGROUND: Recent evolutions of oncologic breast surgery and reconstruction now allow surgeons to offer the appropriate patients a single-stage, autologous tissue reconstruction with the least donor-site morbidity. The authors present their series of buried free flaps in nipple-sparing mastectomies as proof of concept, and to explore indications, techniques, and early outcomes from their series. METHODS: From 2001 to 2011, a total of 2262 perforator-based free flaps for breast reconstruction were reviewed from the authors' prospectively maintained database. RESULTS: There were 338 free flaps performed on 215 patients following nipple-sparing mastectomy, including 84 patients who underwent breast reconstruction with 134 buried free flaps. Ductal carcinoma in situ and BRCA-positive were the most common diagnoses, in 26 patients (30.9 percent) each. The most common flaps used were the deep inferior epigastric perforator (77.6 percent), transverse upper gracilis (7.5 percent), profunda artery perforator (7.5 percent), and superficial inferior epigastric artery flaps (3.7 percent). An implantable Cook-Swartz Doppler was used to monitor all buried flaps. Fat necrosis requiring excision was present in 5.2 percent of breast reconstructions, and there were three flap losses (2.2 percent). Seventy-eight flaps (58.2 percent) underwent minor revision for improved cosmesis; 56 (41.8 percent) needed no further surgery. CONCLUSIONS: Nipple-sparing mastectomy with immediate autologous breast reconstruction can successfully and safely be performed in a single stage; however, the authors are not yet ready to offer this as their standard of care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Five-year results: the initial clinical trial of MammoSite balloon brachytherapy for partial breast irradiation in early-stage breast cancer.

OBJECTIVE: Patients with early-stage invasive ductal breast cancer were prospectively evaluated using MammoSite RTS balloon brachytherapy (RTS Cytyc Corp, Marlborough, MA) as the sole modality for delivering accelerated partial breast irradiation to the lumpectomy bed with breast-conserving surgery. This report presents the 5-year results of the treated patients. METHODS: From May 2000 to October 2001, 70 patients were enrolled in this prospective study. Forty-three patients completed accelerated partial breast irradiation with MammoSite brachytherapy following lumpectomy and axillary staging. Thirty-six patients have been followed for a median of 5.5 years (mean 65.2 months). Criteria for entry into the study were unifocal invasive ductal carcinoma, tumor size < or = 2 cm, age > or = 45 years, absence of extensive intraductal component, cavity size > or = 3 cm in 1 dimension, node-negative, and final margins negative per National Surgical Adjuvant Breast and Bowel Project definition. A minimum balloon-to-skin surface distance of 5 mm was required. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose-rate brachytherapy. Data on infection, seromas, cosmetic outcome, and toxicities were collected at 3 and 6 months and at yearly intervals. Local recurrences, both true recurrences in the lumpectomy bed and failures outside the initially treated target volume (elsewhere failures), were recorded. Contralateral breast failure rates were noted. RESULTS: The catheter was not implanted in 16 of the 70 enrolled patients due to cavity size not amenable to balloon placement (n = 10), ineligible by criteria (n = 4), and skin spacing (n = 2). Fifty-four patients were implanted and 43 were successfully treated with MammoSite balloon brachytherapy. Reasons for catheter explantation in 11 patients were poor cavity conformance in 7, inadequate skin spacing in 2, positive node in 1 and age less than 45 years in 1. Of the 43 patients who completed treatment, the infection rate was 9.3%. Seroma formation occurred in 32.6% of patients, of which 12% were symptomatic requiring aspiration. Asymptomatic fat necrosis was identified in 4 of the 43 patients, noted from time of catheter removal at 11, 14, 42, and 63 months. Good-excellent cosmetic outcomes were achieved in 83.3% of the 36 patients with more than 5 years of follow-up. Cosmetic outcomes were improved, with increased skin spacing having statistical significance at skin spacing > or = 7 mm. The only serious adverse events were 2 infections: mastitis and abscess. Seven of the 43 treated patients have been discontinued from follow-up. None had a local recurrence recorded at last visit. Reasons for exit from the study were death from metastatic disease (n = 3), lost to follow-up (n = 2), and placed in hospice for other medical conditions (n = 2). No local recurrences (either at the tumor bed or elsewhere in the breast) or regional recurrences have occurred in the 36 patients who have been followed for a median of 5.5 years. No contralateral cancers have developed. CONCLUSIONS: MammoSite balloon brachytherapy as a sole modality for delivering radiation to the tumor bed has been successful in achieving excellent local control in this initial clinical study of patients with early-stage invasive ductal breast cancer. This has been achieved with minimal toxicities and good-excellent cosmetic outcomes in 83.3%. Accelerated partial breast irradiation using the MammoSite balloon in a carefully selected group of patients has demonstrated 5-year local recurrence results comparable to those achieved with conventional whole breast radiation therapy and interstitial catheter brachytherapy as reported at 5-year data points in studies of these treatment modalities. Poor cavity conformance and inadequate skin distance were the main factors limiting use of the MammoSite device. Extended follow-up will be required to determine the long-term efficacy of this treatment modality.

A phase I/II trial of 125I methylene blue for one-stage sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy can be associated with delays in operating room schedule and with significant pain during the preoperative Tc colloid injection. To avoid these problems, we developed a novel radiolabeled blue dye that can be injected intraoperatively. METHODS: We performed a phase I/II trial (IND#70627) of sterile pyrogen-free I-methylene blue to identify sentinel nodes in patients with breast cancer. Twelve women were studied. Two women each were given peritumoral or circumareolar injections of 100, 200, 300, 400, 500, or 1000 microCi of I methylene blue. RESULTS: Sentinel nodes were detected in 11 of 12 patients, with a low-dose 200 microCi patient being the single exception. The number of sentinel nodes detected per patient ranged from 0 to 3 (mean = 1.66 nodes/case). Radioactivity at the tumor injection site [counts per second (cps) averaged over 10 seconds] ranged from 3346 to 47,300 cps and was highly dose-dependent (r = 0.90, P = 0.0002). In contrast, the in vivo node counts ranged from 0 to 1228 cps, while ex vivo counts ranged from 0 to 1516 cps. The in vivo nodal counts were dose-dependent (r = 0.67, and P = 0.0231). Radiation was carefully monitored inside the operating room and in pathology. Even with the 1-mCi dose, the radioactive blue dye produced significantly lower personnel exposure than historically seen with Tc. CONCLUSIONS: This method eliminates the painful preoperative injections of Tc colloid, is performed by the surgeon in the operating room, is associated with lower radiation exposures for personnel, and avoids the delays caused by nonoperating room personnel. These observations warrant a more extensive trial of this method using the 1000-microCi dose of I methylene blue dye for sentinel lymph node biopsies.

Postlumpectomy Insertion of the MammoSite brachytherapy device using the scar entry technique: initial experience and technical considerations.

For women undergoing breast-conserving surgery, recent reports suggest that in selected cases accelerated partial breast irradiation may yield results equal to that of whole breast irradiation. Over 31 months, 19 patients underwent accelerated partial breast irradiation using the MammoSite as the sole radiation treatment following breast-conserving surgery. Seventeen patients had the MammoSite inserted postoperatively using the scar entry technique (SET). Treatments were delivered using high dose rate iridium 192 given twice a day for 5 days. Three complications (two minor, one major) occurred. Late radiation morbidity and overall cosmetic results were evaluated. Eighty percent of patients had either no change from baseline or slight change in skin pigment. More than 90% had good or excellent overall cosmetic outcomes. Patients undergoing accelerated partial breast irradiation with the MammoSite inserted using SET had excellent overall cosmetic results. Advantages of the SET over intraoperative placement are presented.