Axillary Response in Patients Undergoing Neoadjuvant Endocrine Treatment for Node-Positive Breast Cancer: Systematic Literature Review and NCDB Analysis.

BACKGROUND: Several studies have proven that neoadjuvant endocrine therapy (NET) has a similar beneficial therapeutic effect in estrogen-positive (ER+) breast cancer (BC) with improved breast conservation rate in patients undergoing NET versus neoadjuvant chemotherapy (NAC). The impact of axillary complete pathologic response (pCR) is less clear. We evaluate the impact of NET on axillary downstaging and surgical management. METHODS: Using the National Cancer Database (NCDB), we identified all patients with node positive (N+), ER+, HER2- BC undergoing NET and performed a systemic review of literature using PRISMA guidelines. RESULTS: The literature review identified 1479 clinically N+ patients in four studies, 148 of whom had axillary pCR (10.0%). In the two studies of patients with invasive lobular carcinoma (ILC), 7.8% (69/883) of clinically N+ patients had axillary pCR. The NCDB query identified 4580 female patients with clinically N+ ER+ HER2- BC who underwent NET from 2010 to 2016 with mean age of 61.4 years. Patients who achieved a pCR were more likely to have N1 disease (p 0.008), moderately differentiated tumors (p 0.003), and ductal histology (p 0.04). There was no statistically significant difference in race, comorbidity score, education, income, hospital setting, or clinical tumor stage. Of the 4580 total patients, 663 (14.48%) had an axillary pCR (pN0) after NET, and 3917 (85.52%) remained pN+. CONCLUSIONS: We found that patients who underwent NET for N+ disease had a higher axillary pCR than previously reported (10%) in smaller studies. Although NET is not a common treatment option for women with N+ ER+ HER2- BC, it may be a suitable option for axillary downstaging, which is currently underutilized.

Two-Stage Prosthetic Breast Reconstruction: A Comparison Between Prepectoral and Partial Subpectoral Techniques.

BACKGROUND: Prosthetic breast reconstruction with prepectoral placement may confer clinical advantages compared with subpectoral placement. The purpose of this study was to assess and compare clinical outcomes following 2-stage reconstruction following prepectoral and partial subpectoral placement of tissue expanders and implants. METHODS: A retrospective review of 39 (prepectoral) and 50 (partial subpectoral) patients was completed. Acellular dermal matrix was used in all patients. Mean age was 50.4 and 49.2 years, respectively. Body mass index (BMI) > 30 was noted in 15.4% of prepectoral and 18% of partial subpectoral patients. Radiation therapy was delivered to 38.5% of prepectoral patients and to 22% of partial subpectoral patients. Mean follow-up was 8.7 and 13 months for the prepectoral cohort and partial subpectoral cohorts. RESULTS: The percentage of patients having at least 1 adverse event was 20.5% in the prepectoral and 22% in the partial subpectoral cohorts. The incidence of surgical-site infection and seroma was 8.1% and 4.8%, respectively, for the prepectoral cohort and 4.8% and 2.4%, respectively, for the partial subpectoral cohorts. Device explantation was 6.5% for the prepectoral and 7.2% for the partial subpectoral patients. Explantation did not occur in patients who had radiation or who had a BMI > 30. Four patients (6 breasts-7.2%) required conversion from partial subpectoral to prepectoral because of animation deformity. CONCLUSIONS: Prepectoral reconstruction is a viable alternative to partial subpectoral reconstruction. Proper patient selection is an important variable. Prepectoral reconstruction can be safely performed in patients with a BMI < 40 and in patients having postmastectomy radiation therapy.

The biplanar oncoplastic technique case series: a 2-year review.

BACKGROUND: Oncoplastic techniques for breast reconstruction following partial mastectomy are now commonly included in the armamentarium of most reconstructive plastic surgeons. These techniques have been frequently used for women with large breast volume and less frequently used form women with small to moderate breast volume. Most women with smaller breast volumes have been typically considered for mastectomy. As an alternative to mastectomy, the biplanar technique was designed and described as an oncoplastic option. The purpose of this manuscript is to review our 2-year experience using this technique in a series of women with small to moderate breast volume. METHODS: A retrospective review of patients who underwent oncoplastic surgery from 2011-2012 by the senior authors (RM and MYN) was completed. Ten patients were identified that had the biplanar technique involving glandular tissue rearrangement in conjunction with the immediate placement of a submuscular implant or tissue expander. Patient demographics, perioperative details, and post-operative outcomes were evaluated. RESULTS: The mean age and BMI of the ten patients in the study was 56 years (range, 40-68 years) and 24.1 years (range, 20.3-28.6 years) respectively. The mean resection volume was 76.5 g (range, 25-164 g). Eight patients had placement of a permanent implant and two patients had placement of a tissue expander. The average volume of the implanted devices was 138 cc (range, 90-300 cc). In eight patients, a sheet of acellular dermal matrix was used. Immediate biplanar reconstruction was performed in seven patients and a staged-immediate biplanar reconstruction was performed in three patients. Complications included a positive margin on final pathology requiring mastectomy (n=1), infection (n=1), incisional dehiscence following radiation (n=1), and loss of nipple sensation (n=2). Follow-up ranged from 4.5-27 months (mean of 19.5 months). CONCLUSIONS: The biplanar oncoplastic technique may represent a valuable option in women with small to moderate breast volumes that choose to have breast conservation therapy (BCT). This technique has demonstrated success with minimizing contour irregularities and maintaining breast volume. Based on our early experience, patient satisfaction is favorable.

Biplanar oncoplastic surgery: a novel approach to breast conservation for small and medium sized breasts.

UNLABELLED: Biplanar oncoplastic surgery represents a novel technique with which to address partial breast reconstruction defects in small to medium sized breasts. Traditional oncoplastic volume displacement techniques may correct contour irregularities but do not address volumetric asymmetries. Volume replacement techniques classically rely on autologous tissue flaps. A biplanar approach, with a combination of glandular rearrangement techniques and volume enhancement with submuscular implants, can result in an alternative approach in select patients to achieve symmetry. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Nipple-sparing mastectomy for prophylactic and therapeutic indications.

BACKGROUND: Nipple-sparing mastectomy remains controversial and its adoption has been slow because of oncologic and surgical concerns. METHODS: A retrospective study evaluated all nipple-sparing mastectomies performed at a single institution for therapeutic or prophylactic indications for which records were available. RESULTS: Between 1989 and 2010, 162 nipple-sparing mastectomies were performed in 101 women. Forty-nine (30 percent) were performed for therapeutic purposes on 48 patients. A subareolar biopsy specimen was taken in 39 of 49 breasts (80 percent); four (10 percent) revealed ductal carcinoma in situ, and the nipple or nipple-areola complex was later removed. Four of 49 breasts (8 percent) in the therapeutic group had ischemic complications involving the nipple-areola complex, one of which (2 percent) was excised. With a mean follow-up of 2 years 6 months (range, 5 months to 9 years 5 months), no patients developed cancer in the nipple-areola complex. The remaining 113 mastectomies (70 percent) were performed prophylactically on 80 patients. The subareolar tissue was biopsied in 80 breasts (71 percent). One biopsy revealed lobular carcinoma in situ; none had ductal carcinoma in situ or invasive cancer. Two nipple-areola complexes (1.8 percent) were ischemic and excised. With a mean follow-up of 3 years 7 months (range, 5 months to 20 years 6 months), no patients developed new primary cancers in the nipple-areola complex. CONCLUSIONS: Nipple-sparing mastectomy can be safe in properly selected patients. A subareolar biopsy can effectively identify nipple-areola complexes that may harbor cancerous cells. Ischemic complications resulting in nipple loss can be minimized, and long-term follow-up suggests that this technique deserves further investigation in properly selected patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Mutagen sensitivity, tobacco smoking and breast cancer risk: a case-control study.

UNLABELLED: Given the high incidence of breast cancer and that more than half of cases remain unexplained, the need to identify risk factors for breast cancer remains. Deficiencies in DNA repair capacity have been associated with cancer risk. The mutagen sensitivity assay (MSA), a phenotypic marker of DNA damage response and repair capacity, has been consistently shown to associate with the risk of tobacco-related cancers. METHODS: In a case-control study of 164 women with breast cancer and 165 women without the disease, we investigated the association between mutagen sensitivity and risk of breast cancer using bleomycin as the mutagen. RESULTS: High bleomycin sensitivity (>0.65 breaks per cell) was associated with an increased risk of breast cancer, with an adjusted odds ratio of 2.8 [95% confidence interval (CI) = 1.7-4.5]. Risk increased with greater number of bleomycin-induced chromosomal breaks (P(trend) = 0.01). The association between bleomycin sensitivity and breast cancer risk was greater for women who were black, premenopausal and ever smokers. Our data also suggest that bleomycin sensitivity may modulate the effect of tobacco smoking on breast cancer risk. Among women with hypersensitivity to bleomycin, ever smokers had a 1.6-fold increased risk of breast cancer (95% CI = 0.6-3.9, P for interaction between tobacco smoking and bleomycin sensitivity = 0.32). CONCLUSIONS: Increased bleomycin sensitivity is significantly associated with an increased risk of breast cancer in both pre- and postmenopausal women. Our observation that the effect of tobacco smoking on breast cancer risk may differ based on mutagen sensitivity status warrants further investigation.

Phytohemagglutinin-induced mitotic index in blood lymphocytes: a potential biomarker for breast cancer risk.

BACKGROUND: Cell proliferation is associated with the pathogenesis of cancer because it provides opportunities for accumulating genetic mutations. However, biomarkers of cell proliferation in response to environmental stimuli have not been adequately explored for breast cancer risk. METHODS: In a case-control study of 200 breast cancer patients and 360 healthy controls, we investigated the association between phytohemagglutinin (PHA)-induced mitotic index in blood lymphocyte and breast cancer risk. RESULTS: Having high mitotic index (>3.19%) was associated with an increased risk of breast cancer, with adjusted odds ratios (95% confidence interval) of 1.54 (1.03-2.30) and 2.03 (1.18-3.57) for all women and post-menopausal women, respectively. Mitotic index was correlated with some reproductive factors and body mass index in controls. CONCLUSIONS: Our data suggest increased PHA-induced mitotic index in blood lymphocytes is associated with an increased breast cancer risk and that this association may be modulated by reproductive and other hormones.

Nipple-sparing mastectomy.

BACKGROUND: The debate over nipple-sparing mastectomy continues to evolve. Over the past several years, it has become more widely accepted, especially in the setting of prophylactic mastectomy, but its role in the treatment of breast cancer has only recently been reexamined. METHODS: Two indications for the procedure are discussed: prophylactic, for the high-risk patient; and the more controversial topic, therapeutic nipple-sparing mastectomy, for the patient with breast cancer. A review of the literature suggests that certain breast cancers may be amenable to retaining the nipple if they meet specific oncologic criteria: tumor size 3 cm or less, at least 2 cm from the nipple, not multicentric, and with clinically negative nodes. Moreover, newer technologies such as magnetic resonance imaging and preoperative mammotome biopsy may make the procedure even safer in this setting. Practical and technical aspects of the procedure are discussed, including patient selection. RESULTS: The accumulating data from multiple series of nipple-sparing mastectomy show that properly screened patients have a low risk of local cancer recurrence, that recurrences occur rarely in the nipple, and that recurrences in the nipple can be managed by removing the nipple. CONCLUSIONS: Despite continued controversy and the need for more long-term outcome data, nipple-sparing mastectomy is a procedure that is gaining increasing visibility and acceptance. Provided that certain oncologic and practical criteria are applied, it has the potential for allowing less invasive surgery and improved cosmetic outcomes without increased oncologic risk in appropriately selected patients.

Screening and follow-up of the patient at high risk for breast cancer.

Accurately defining a patient's risk of developing breast cancer is a challenging endeavor. Many factors have been implicated in the causation of breast cancer and quantifying them is difficult. Risk stratification is performed using population models, such as the Gail model, as well as the patient's personal and family history and genetic testing. The clinician who is facile with these components will not only be able to identify those patients at highest risk for whom heightened surveillance is recommended, but also to allay the fears of the average-risk patient and provide them reassurance. Patients who are at very high risk of developing breast cancer are BRCA1 or BRCA2 gene mutation carriers, those with a personal history of atypical ductal hyperplasia or lobular carcinoma in situ with associated family history, those who have undergone therapeutic or similarly significant radiation exposure, and those with a history of a BRCA1 or BRCA2 gene mutation in the family of an untested individual. Patients with an elevated risk, but not in the very high risk category, are those with a family history of breast cancer, personal history of breast cancer, significantly dense breast tissue, hormone replacement therapy longer than 10 years, and a history of atypical ductal hyperplasia or lobular carcinoma in situ without family history of breast cancer. Risk-reducing strategies include chemoprevention with tamoxifen or raloxifene and surgical prophylaxis with bilateral prophylactic mastectomy and/or bilateral salpingo-oophorectomy. A high-risk surveillance regimen includes annual mammography, annual magnetic resonance imaging in selected individuals, and semiannual clinical breast exams.

A single institution review of new breast malignancies identified solely by sonography.

BACKGROUND: The role of sonography as a sole identifier of breast malignancy remains undetermined. Currently, the American College of Radiology Imaging Network (ACRIN) trial, protocol 6666, is accruing high risk patients, with dense breast tissue on mammography, to evaluate the performance of screening sonography. STUDY DESIGN: We conducted a retrospective single institution review to identify the detection rate of nonpalpable, mammographically occult breast malignancies identified solely by sonography. RESULTS: A total of 34,694 breast sonograms were performed at our outpatient radiology affiliate between April 1998 and April 2006. This number includes unilateral and bilateral examinations, and, 6-month followup examinations. Computerized databases and individual charts were retrospectively reviewed. Sonographic and mammographic findings were compared to determine concordance of identified lesions. Four thousand ninety-one ultrasound guided biopsies, (fine needle aspiration biopsy [FNA] and core needle biopsy [CNB]) were performed over the 8-year period, and 452 malignancies were identified. Discarded fluid contents of pure cyst aspirations were not included in this number. Seven percent (32) of the biopsy-proved malignancies were mammographically occult, of which 59% (19) were palpable, and 31% (10) were not palpable. Of all cancers diagnosed, 2.2% were identified solely by sonography. The number of cancers identified solely by sonography relative to the total number of sonograms done was 0.03%. CONCLUSIONS: Given these results, we advocate the selective use of sonography in appropriate populations, namely, in those with palpable findings, mammographic abnormalities, and in women with dense tissue who have personal or family history of breast cancer.

Less is more: transmammary axillary lymph node evaluation: an initial clinical experience.

BACKGROUND: Standard axillary node dissection has the potential to cause a significant amount of morbidity. Sentinel lymph node biopsy has considerably decreased this rate of morbidity; however, data recently presented, based on ACOSOG Z-10, suggest that even this less invasive technique can have a lymphedema rate as high as 7%. The transmammary axillary lymph node evaluation procedure (TANE) removes the sentinel node via the breast incision, thus eliminating the axillary incision. This may decrease morbidity, including lymphedema, dyesthesias, pain, and loss of range of motion, and it will also improve cosmetic outcome. METHODS: This is a prospective observational study to determine if it is feasible to perform both the partial mastectomy and sentinel lymph node biopsy via a single incision. All patients were consented for a partial mastectomy and sentinel lymph node biopsy. The partial mastectomy was performed in the standard fashion. The sentinel lymph node biopsy was performed via the same incision either before or after the breast specimen was removed. The sentinel lymph node biopsy was then performed in the standard fashion. RESULTS: The TANE method was attempted in 44 patients from June 2005 to March 2006 and was successful in 43, for a rate of 97.73%. The mean age of the patients was 57.6 years, with a range of 34 to 82 years. The average tumor size was 1.57 cm, with a range of 0.4 cm to 4.5 cm. The TANE procedure was performed most often in patients with tumors located in the upper outer quadrant (79.54%). There were no perioperative complications. CONCLUSION: Our prospective study showed that this is a feasible procedure for sentinel lymph node biopsy and axillary lymph node dissection. The number of sentinel and axillary nodes obtained was within the standard published norms. Our technical success rate was 97.33%, and we did not have any perioperative complications. In this pilot study, there was the cosmetic benefit of only 1 incision. Future studies will examine if the TANE procedure can objectively decrease morbidity compared to a separate axillary incision.