Nazanin Khakpour

Selective use of sentinel lymph node surgery during prophylactic mastectomy

Patients with invasive cancer identified at the time of prophylactic mastectomy (PM) will require axillary lymph node dissection for staging; therefore, many surgeons advocate sentinel lymph node (SLN) surgery at the time of PM. The current study investigates the invasive cancer rate in PM and evaluates factors associated with invasive cancer to guide SLN surgery use.

Factors associated with improved outcome after surgery in metastatic breast cancer patients

BACKGROUND Recent studies suggest local surgical therapy improves survival in metastatic breast cancer (MBC). We evaluate the difference in outcome in patients with MBC after mastectomy versus breast conservation (BCT) and factors that influence outcome. METHODS In a retrospective review of our prospective database, we identified patients who presented with MBC (1990 to 2007). Patient surgery type and clinicopathologic factors were reviewed. We compared OS between pts dependent on surgery and clinicopathologic factors. RESULTS Of the 566 patients with MBC, 154 (27%) underwent removal of the primary tumor. Surgery was associated with an improved OS (33%) versus no surgery (20%) (P = 0.0015). Of those undergoing local therapy; mastectomy was associated with a 37% OS vs BCT with a 20% OS (P = 0.04). CONCLUSIONS Our study confirms that removal of the primary tumor in MBC is associated with improved overall survival. It appears that mastectomy is associated with a significantly improved overall survival.

The presence of extensive retraction clefts in invasive breast carcinomas correlates with lymphatic invasion and nodal metastasis and predicts poor outcome: a prospective validation study of 2742 consecutive cases.

We previously reported that the presence of extensive retraction clefts (RC) in breast cancers correlates with increasing tumor size and grade as well as lymphatic tumor spread and predicts poor outcome. This study is a prospective validation of our prior results. Consecutive cases of invasive breast carcinoma (n=2742) were reviewed to determine the diagnoses, including histologic type, grade, presence of lymphovascular invasion (LVI), and extent of RC. No differences were found in the extent of RC between corresponding core needle biopsy and surgical samples. Extent of RC showed a significant correlation with tumor size, grade, LVI, and nodal metastasis in both core needle biopsy and surgical specimens. These associations remained significant in subset analyses of small (⩽1 cm), node-negative and node-positive tumors. Extensive RC predicted poor recurrence-free (P<0.0001) and overall (P<0.0001) survival and remained significant in subset analyses of node-negative (P=0.0015 and 0.0021, respectively) and node-positive (P=0.0039 and 0.0214, respectively) cases. Carcinomas without LVI but extensive RC were associated with better outcome than carcinomas with LVI but worse than those without LVI and low RC. This prospective study confirms that the presence of extensive RC in invasive breast carcinomas correlates with aggressive tumor features and lymphatic tumor spread. Extensive RC appears to be an independent factor predictive of poor outcome in node-negative and node-positive disease. Our results support the hypothesis that RCs are the morphologic reflection of biological changes in tumor cells playing a role in lymphatic tumor spread and likely represent an early stage of LVI with similar clinical implications.

Ipsilateral nodal recurrence after axillary dissection for breast cancer

INTRODUCTION Level I/II axillary lymph node dissection (ALND) is the standard operation for patients with node-positive breast cancer. The objective of this study was to assess the incidence of regional nodal recurrence (RNR) after ALND performed for definitive operative treatment for primary breast cancer. MATERIALS AND METHODS A retrospective, Institutional Review Board-approved query of our single-institution National Comprehensive Cancer Network database was performed for patients undergoing ALND who developed subsequent RNR. All patients were treated from 1999 to 2009. A detailed chart review was performed and clinical, pathologic, treatment, and outcome data were collected. RESULTS A total of 1614 patients had an ALND for initial staging; 14/1614 (0.9%) patients had RNR. Two other patients had contralateral breast/axillary recurrences and were excluded. The mean age at diagnosis for the sample group was 52.7 y (range 34-77); mean follow-up time was 47.1 mo (range 12.6-114.6). The median number of nodes for ALND was 16 (range 8-27). The median number of positive nodes was 2.5 (range 0-7). Nine (64.3%) cases were estrogen receptor/progesterone receptor negative. Twelve (85.7%) patients had axillary recurrences, and six of 12 (50.0%) had concurrent chest wall lesions. Twelve patients (85.7%) had distant metastases; nine of 12 (75.0%) died; two were lost to follow-up. Mean time from RNR to distant recurrence was 6.0 mo (range 0-29.3 mo). CONCLUSIONS RNR after ALND is rare but a harbinger of poor outcome. This is apparent regardless of treatment used for initial disease or recurrence. Specifically, RNR after primary ALND is related to increased risk of mortality and distant metastatic disease.

Axillary burden of disease following false-negative preoperative axillary evaluation

BACKGROUND Preoperative axillary ultrasound (AUS) and fine-needle aspiration (FNA) are sensitive and specific for breast cancer nodal metastases. We hypothesize that false-negative result predicts minimal axillary disease (≤2 +nodes). METHODS A retrospective review of breast cancer patients receiving AUS identified T1/T2 tumors and positive sentinel node with axillary dissection. Chi-square analysis was performed using Fishers exact test. RESULTS Of 903 AUS cases, 384 had T1/T2 tumors. False-negative rate of AUS ± FNA was 48% and 45%, respectively. Of 384 cases, 73 were sentinel node positive and had axillary dissection; 55 (75.3%) were invasive ductal carcinoma (IDC). Negative predictive value for greater than or equal to 2 nodes was 71% in IDC versus 44% for in non-IDC patients. Sixteen (29.0%) IDC patients had greater than or equal to 3 positive nodes versus 10 (55.5%) non-IDC (P = .05) patients. CONCLUSION The high negative predictive value for AUS with FNA for IDC suggests that the AUS plus FNA interpretation may be better limited to the ipsilateral nodes of IDC.

Pathologic Tumor Response of Invasive Lobular Carcinoma to Neo‐adjuvant Chemotherapy

Abstract:  Neo‐adjuvant chemotherapy is used for locally advanced breast cancer patients with significant variation in tumor response. Our objective is to determine the clinicopathologic effect of neo‐adjuvant chemotherapy on invasive lobular carcinoma. A review of a single‐institution data base of women diagnosed with breast cancer identified 30 patients from 1999 to 2009 with operable invasive lobular carcinoma who received neo‐adjuvant chemotherapy. Patient demographics and clinicopathologic data were reviewed. Cases were reviewed by a single pathologist (NNE). Residual cancer burden class was determined for each case. Median patient age was 50 years (range 25–79). All tumors were hormone receptor positive and clinical stage II or III carcinomas. Most patients (53.3%) had combination anthracycline‐ and taxane‐based chemotherapy. Therapy‐related changes were noted within the tumor bed in 25 (83.3%) patients. Six (30%) of 20 patients with residual axillary disease had therapy‐related nodal changes. There were 11 patients with moderate residual disease (class II) and 18 (60%) with extensive (class III); there were no complete pathologic responses (class 0). Only one patient (3.3%) converted from mastectomy to breast‐conserving surgery. Four (13.3%) patients developed distant metastases; all had pleomorphic‐type, clinical stage III tumors with residual cancer burden III classification and developed distant disease in the 2 years after surgery (range 0–26 months). Median follow‐up time was 29.5 months (range 7–132). Patients with locally advanced pleomorphic‐type lobular carcinoma appear to develop early post‐treatment metastatic disease. Neo‐adjuvant chemotherapy did not appear to have significant impact on the surgical treatment of patients with invasive lobular carcinoma.

Early experience with ultrasound features after intrabeam intraoperative radiation for early stage breast cancer

Intraoperative radiation therapy (IORT) is an emerging option for partial breast radiotherapy in select women with early stage breast cancer. We assessed short‐term clinical and sonographic findings after breast conservation (BCT) and IORT.

Comparison of breast magnetic resonance imaging clinical tumor size with pathologic tumor size in patients status post-neoadjuvant chemotherapy

BACKGROUND Neoadjuvant chemotherapy (NACT) is used in breast cancer to evaluate the response to treatment. We examined the usefulness of breast magnetic resonance imaging (MRI) in the evaluation of tumor response after NACT. METHODS Breast MRIs of 87 women with MRI after NACT were reviewed. The Spearman coefficient was used for estimating the correlation between MRI and pathologic tumor sizes (ypTs). RESULTS The median age was 50 years (range 25 to 83 years). The median MRI size was 1.25 cm (range 0 to 10 cm). The median ypT was 1.20 cm (range 0 to 10.4 cm). The Spearman coefficient between MRI and ypT was .78 (95% confidence interval, .67 to .85; P < .0001). MRI was found to have a positive predictive value of 92% and a negative predictive value of 64% for residual in-breast disease. The sensitivity and specificity of MRI were 86% and 77%, respectively. CONCLUSIONS MRI correlates well with the final pathology and can be a useful modality to predict residual disease after NACT and aid in surgical planning.

Magnetic Resonance Imaging for Axillary Breast Cancer Metastasis in the Neoadjuvant Setting: A Prospective Study

Background: Breast magnetic resonance imaging (MRI) for assessment of regional breast cancer metastasis is controversial owing to the variable specificity. We evaluated breast MRI for axillary metastasis in neoadjuvant chemotherapy patients. Materials and Methods: A single‐institution, institutional review board–approved prospective trial enrolled female breast cancer patients receiving neoadjuvant chemotherapy from 2008 to 2012 and collected the pre‐ and post‐treatment MRI, pretreatment axillary ultrasound, axillary biopsy, and surgical pathologic findings. The kappa coefficient was used to evaluate the strength of the agreement between the 2 modalities and Fishers exact test was used to evaluate the association. Results: A total of 43 patients were included. Of these 45 patients, 35 had stage N1‐N2 before treatment. Comparing the abnormal results on the pretreatment MRI scans and axillary biopsy examinations, a consistent diagnosis was found for 92%, with a moderate strength of agreement (kappa coefficient, 0.54). The pretreatment MRI findings were significantly associated with the axillary biopsy results (P = .014). The false‐positive rate, false‐negative rate, sensitivity, and specificity were 50%, 3%, 97%, 50%, respectively. Comparing the post‐treatment MRI and surgical pathologic findings revealed a consistent diagnosis rate of, with a slight strength of agreement (kappa, 0.16). The false‐positive rate, false‐negative rate, sensitivity, and specificity were 38%, 46%, 55%, and 63%, respectively. The post‐treatment MRI findings were not associated with the pathologic lymph node results (P = .342). Conclusion: Pretreatment breast MRI was more specific for axillary metastasis than was axillary ultrasonography. However, post‐treatment breast MRI was not predictive of residual axillary disease and should be used cautiously when altering treatment plans. Micro‐Abstract: Evaluation of the axilla on breast magnetic resonance imaging (MRI) for breast cancer is a growing practice. We reviewed a prospective breast cancer cohort undergoing neoadjuvant chemotherapy to compare the pretreatment breast MRI findings with the axillary ultrasound/fine needle aspiration findings and the post‐treatment breast MRI findings with the surgical pathologic findings. The prechemotherapy MRI findings were more specific for axillary metastasis than were the focused ultrasound findings. However, the postchemotherapy MRI findings were not predictive of residual axillary disease.

Upright, Standing Technique for Breast Radiation Treatment in the Morbidly-Obese Patient

To the Editor: Many women with early-stage breast cancer receive mastectomy when they could be ‘‘potential’’ candidates for breast conservation therapy (BCT). Smitt et al. reported that while 46% of patients have a medical or personal contraindication to BCT, the rest could use specialty consultation (1). Morbidly obese patients are a particularly vulnerable population in cancer care. The incidence of female obesity in the US has risen greatly, and obesity is a known barrier to screening and radiation treatment in breast and gynecological malignancies (2–4). Radiation therapy may not be offered because of more side-effects. For example, body mass index predicts for an increased incidence of radiation pneumonitis in breast cancer patients (5). Newer techniques like prone positioning allow the breast to hang away from the chest wall and decrease moist desquamation in the skin folds. Unfortunately, whether lying supine or prone on the linear accelerator treatment couch, the patient can only receive radiation if she does not exceed the weight limitation of the equipment. The only other treatment option is mastectomy. We report on a morbidly obese, 37-year-old African-American woman who refused mastectomy and was treated using BCT. She presented with a bulging, palpable mass without nipple or skin involvement. Mammogram revealed a highly dense, mostly circumscribed 9 cm mass in the 12–1 o’clock position of the right breast without any associated calcifications. The ultrasound described a superficial, lobulated cyst, and aspiration of 160 mL of blood-tinged fluid was positive for malignancy. She was seen in the multi-disciplinary setting. On physical exam, she was 165 cm tall (5¢4¢¢) and weighed 186 kg (411 lbs), with a body mass index of 68.5. The weight limitation for the couch of the CT scanner for planning is 400 lbs and for the Varian Trilogy linear accelerator for treatment is 350 lbs. The patient was offered mastectomy with reconstruction or a lumpectomy with interstitial brachytherapy (accelerated partial breast irradiation); however, she refused either treatment option. The patient underwent right breast lumpectomy and sentinel lymph node mapping which revealed a 9.6 cm, poorly differentiated invasive ductal carcinoma that was estrogen, progesterone, and HER-2 ⁄ neu receptor negative with >2.4 cm surgical margins, and no lymphovascular invasion. Both nodes were negative. She was staged as pT3N0, group IIB. She then received adjuvant dose dense adriamycin (60 mg ⁄ m) and cytoxan (600 mg ⁄ m) for four cycles followed by dose dense weekly paclitaxel (175 mg ⁄ m) for four cycles with pegfilgrastim support. She was seen pre and postoperatively by radiation oncology to explore the feasibility of external beam radiation to the right breast in the form of tangents while in the upright, standing position. A carbon fiber stereotactic body board (body frame: baseplate, part#70–2B, 3Dline Medical Systems, Elekta AB, Stockholm, Sweden) measuring 1.5 cm thick was attached to the head of the treatment couch to allow separation of the breast from the patient’s underlying belly. The treatment couch was brought to the level of the inframammary fold. A soft, 20 · 25 cm mold cushion (Moldcare pillow, WFR Aquaplast Corp, Avondale, PA, USA) was secured to the edge of the board to cushion the breast. Opaque wires were placed to mark the patient’s breast borders and the avoidance structures (contralateral breast, ipsilateral arm, and belly). An aquaplast pelvic body cast (Precut Pelvic 6 point Fixation Mask; Part #75–3A, Elekta AB, Stockholm, Sweden) was cut and molded over the breast and affixed to the stereotactic breast board (Fig. 1a). The patient stood with the right breast in position while keeping Address correspondence and reprint requests to: Majid M. Mohiuddin, MD, Department of Radiation Oncology, University of Maryland School of Medicine, 22 S. Greene St, Baltimore, MD 21201, USA, or e-mail: mmohiuddin @umm.edu.