Jeff King

Survival Outcomes in Node-Negative Breast Cancer Patients Evaluated With Complete Axillary Node Dissection Versus Sentinel Lymph Node Biopsy

BackgroundSentinel lymph node (SLN) biopsy combined with microstaging-associated immunohistochemical staining for cytokeratin more accurately assigns patients to their corresponding diagnostic stage. The purpose of this study was to compare the survival outcomes of node-negative patients who received an SLN biopsy with historical control data of node-negative patients who received routine complete axillary lymph node dissection (CALND) in the pre-SLN biopsy era.MethodsUnder institutional review board approval, 2458 node-negative invasive breast cancer patients between the ages of 25 and 94 years (mean, 60 years) were treated at our institution from January 1986 to May 2004. Of these 2458 patients, 604 (25%) were evaluated with CALND, whereas 1854 (75%) were evaluated with SLN biopsy. All were treated according to the current stage-specific guidelines. Kaplan-Meier graphs of overall survival and disease-free survival were constructed for each group of patients, and the two groups were compared by using the log-rank test.ResultsOverall survival and disease-free survival for the CALND and SLN biopsy groups did not differ significantly (P = .98). The average number of lymph nodes extracted in the pre-SLN biopsy group was 18, whereas the average number of SLNs extracted in the post-SLN biopsy group was 3.ConclusionsThe survival rate among node-negative breast cancer patients who received an SLN biopsy alone has proven to have no significant difference (P = .98) from the survival rate among node-negative patients who received a CALND. SLN biopsy alone should replace CALND as the primary tool for axillary staging of breast cancer in node-negative patients.

Sentinel Lymph Node Biopsy in Patients with Previous Ipsilateral Complete Axillary Lymph Node Dissection

BackgroundPrior ipsilateral completion axillary lymph node dissection (CALND) may be considered a contraindication to performing a sentinel lymph node (SLN) mapping in a patient with recurrent breast carcinoma. However, reoperative SLN biopsy following axillary dissection would determine if alternative lymphatic drainage pathways exist. If nodes were found to contain metastatic disease, staging and locoregional control of the disease could be affected.Materials and MethodsAn institutional breast cancer database and electronic health record (IRB No. 102554) prospectively accrued 6225 patients between 1994 and 2007. Under separate IRB approval (IRB No. 102552), this database was queried for patients with a prior history of CALND who received a SLN biopsy. Patients’ demographic, clinical, and treatment variables were recorded.ResultsOf the 6225 patients, 45 (0.7%) were identified as having previously undergone breast-conservation surgery, CALND, and ipsilateral reoperative SLN mapping and biopsy. Of the 45 patients, 13 (29%) had a successful ipsilateral reoperative SLN mapping and biopsy. Nonaxillary drainage was identified in 5 patients with reoperative SLN biopsy.ConclusionReoperative SLN mapping and biopsy is feasible in the setting of local recurrence after previous CALND. This procedure performed for breast cancer recurrence provides important staging information while identifying extra-axillary drainage that could affect both staging and local control.

The surgical treatment of breast cancer in the elderly: a single institution comparative review of 5235 patients with 1028 patients ≥70 years.

Abstract:  As the wave of the baby boomers shifts the age demographic of patients, the current surgical management of breast cancer in elderly women (≥70 years of age) becomes relevant because deviation from standard treatment often occurs in this group. The purpose of this study was to determine the operative mortality when treated with standard surgical procedures and to investigate trends in the surgical management of breast cancer in the elderly. A total of 5,235 patients undergoing either mastectomy or breast conservation surgery (BCS) for invasive and ductal carcinoma in situ (DCIS) were identified in a retrospective review of a prospectively accrued data base between the years of 1994 and 2007 at the Moffitt Cancer Center. Of the 5,235 patients, 1,028 (20%) patients were ≥70 years of age. The 30‐day and 90‐day mortality in the elderly group (age ≥70 years) was 0.2% (95% CI 0.02–0.7%) and 0.7% (95% CI 0.3–1.4%), respectively. The 30‐day and 90‐day mortality among patients <70 years was 0 and 0.05% (2 of 4,207 patients) (95% CI 0.005–0.2), respectively. BCS rates for invasive carcinomas were the highest for patients between 40 and 70 years of age, whereas the mastectomy rates were higher among patients <40 years of age (53%). Elderly women were as likely as women <40 years to have BCS for invasive carcinoma (OR 1.1, 95% CI 0.8–1.5), but more likely to have BCS for DCIS (OR 1.9, 95% CI 1.1–3.3). Surgical mortality in elderly women treated for breast cancer was extremely low and was related to the extent of surgery performed. Breast cancer treatment differed by age groups.

Effects of Prior Augmentation and Reduction Mammoplasty to Sentinel Node Lymphatic Mapping in Breast Cancer

Abstract:  Previous plastic surgery procedures such as breast augmentation or reduction mammoplasty can potentially alter the lymphatic drainage of the breast. The purpose of this study is to determine the success rates of sentinel node lymphatic mapping in patients with previous plastic surgical procedures of the breast. A total of 83 patients with a history of plastic surgery of the breast that underwent subsequent sentinel node mapping between 1996 and 2008 were retrospectively analyzed. Eight‐three patients that underwent a total of 108 sentinel node biopsies. Hundred cases (93%) previously underwent breast augmentation and eight cases (7%) previously underwent reduction mammoplasty. The mean time between the previous plastic surgical procedures and the sentinel node biopsy was 10.3 years (range: 2 months–32 years). Indications for the mapping procedure were invasive cancer (n = 64), ductal carcinoma in situ (n = 17), and prophylactic mastectomy (n = 27). The identification rate of the sentinel node was 95.3% (103/108). The success rate based on type of procedure was 96% (96/100) for augmentation and 87.5% (7/8) for reduction mammoplasty. With a mean follow‐up of 3.4 years, there has been only one local axillary recurrence that occurred at the time of an ipsilateral breast recurrence following lumpectomy. Lymphatic mapping can be successfully performed in patients who have previously undergone plastic surgery operations.

The concept of lymph node dissections in patients with malignant melanoma

Therapeutic lymph node dissections in patients with grossly palpable metastatic melanoma are performed to control regional disease, to salvage a small percentage of patients, and to obtain staging information. Patients with malignant melanoma may undergo elective lymph node dissections, when the basin is clinically negative, for three reasons. There is some evidence based on large retrospective studies that survival is increased in patients with intermediate thickness melanoma if elective lymph node dissections are performed as part of the initial treatment of the primary melanoma. Second, in a small percentage of patients, a previous elective lymph node dissection may have helped control disease in the regional lymphatics, so that more extensive procedures, including amputations, are not necessary. Another important reason is to obtain staging and prognostic information for the patient because most adjuvant protocols are based on the presence or absence of disease in the regional basin. During a 3-year period, 115 patients have undergone a regional nodal dissection at the Moffitt Cancer Center and James Haley VA Hospital as part of their surgical treatment. With a follow-up of 3 years, patients with 1 node positive do significantly better than those with more than 1 node positive in their dissection (p = 0.06). The percentage of nodes positive is also important. Those patients who have less than 10% of their nodes involved with metastatic melanoma have a better survival than those patients whose percentage is greater than 10% (p = 0.07).

COMPUTER DATABASE FOR MELANOMA REGISTRY A Clinical Management and Research Tool to Monitor Outcomes and Ensure Continuous Quality Improvement

The need for an efficient method of handling data is more apparent today in medical practice than at any time in the past. This PC-based database helps with the daily collection, filing, storage, and abstraction of data for clinical management and research. The program also provides a mechanism for continuous quality assessment to monitor clinical standards of care and make interventions to improve the care of the melanoma patient.

Adenoid Cystic Carcinoma of the Breast: A Review of a Single Institution’s Experience

To the Editor: Adenoid cystic carcinoma of the breast (ACCB) is rare, comprising less than 0.1% of breast cancers, and may be under-reported due to misclassification (1). Such misclassification has negative impact, as this tumor requires different clinical management when compared to breast adenocarcinoma. We reviewed our institutional experience by searching a prospectively accrued database of 17,703 patients from 1989–2006 for ‘‘cylindroma,’’ ‘‘cribriform,’’ ‘‘papillary,’’ or ‘‘adeno’’ to minimize misclassification. After histological confirmation, records were reviewed for presentation, staging, therapy, and outcome. Eighty-eight potential patients with ACCB were identified, but after slide review, only seven true ACCB cases were identified (Table 1). Six patients presented with either breast pain or palpable mass. Median age was 49 years (range 37–82 years) and median tumor size was 1.8 cm (range 1.3–5 cm). Imaging studies included mammography in all seven patients that revealed spiculated masses, and ultrasonography in six patients that revealed hypoechoic, well-circumscribed masses. Diagnosis of ACCB was made by core biopsy in one patient and excisional biopsy in six patients performed prior to referral to our institution. Definitive surgery included partial mastectomy in four and total mastectomy in three patients. While at operative resection all lesions appeared grossly wellcircumscribed, histological analysis revealed microscopic tumor extending away from the gross margin, requiring re-excision in all who underwent partial mastectomy. While acceptable margin width has not been definitively established, a minimum of one millimeter seems advisable due to the high rate of margin positivity in this study, and the local recurrence rates of 30–40% reported previously (2). Histologically, ACCB appeared different from the common forms of breast cancer and similar to adenoid cystic carcinomas seen in the head and neck (Fig. 1). The tumor is characterized by a mixture of proliferating epithelial cells forming ductule-like structures and glands (true lumina), and modified myoepithelial elements forming cribriform spaces (‘‘pseudolumens’’). In our series, all but one of our patients underwent sentinel node biopsy, with one patient having isolated tumor cell clusters in the sentinel node detected on IHC only. For this patient, on complete node dissection, the remaining 21 nodes were all negative. In review of the literature, axillary involvement appears in approximately 15% (3). While routine complete node dissection in modern practice is unwarranted, consideration for the low morbidity procedure of a sentinel lymph node biopsy should be given. Omission of sentinel node biopsy in the absence of palpable axillary disease can be weighed on an individual basis. As in our series, this includes small, medial tumors in patients with significant co-morbidity. The follow-up of patients included a clinical examination every 6 months for 5 years, and mammography every 6 months for 2 years and annually thereafter. The three patients treated with partial mastectomy received adjuvant whole breast radiation (range 50– 65 Gy). None of the seven patients received adjuvant hormonal or chemotherapy. All seven tumors were estrogen receptor, progesterone receptor, and HER2 ⁄ neu negative. Despite the ‘‘triple negative’’ hormone receptor status and histological similarity to the clinically aggressive adenoid cystic carcinomas of the head and neck, ACCB had an indolent clinical course. At a median follow-up of 49 months after resection, only one patient had a local recurrence. This patient initially presented to an outside institution and Address correspondence and reprint requests to: Christine Laronga, MD, Comprehensive Breast Program, 12902 Magnolia Drive, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, or e-mail: Christine. Laronga@moffitt.org

Abstract P6-09-45: Long-term follow-up of early stage breast cancer patients with results of MammaPrint®, Oncotype DX® and MammoStrat® risk classification assays

Introduction: The use of genomic tests for the prediction of breast cancer recurrence is becoming more common. MammaPrint® (MP, Agendia Inc.) is a 70-gene microarray assay designed to assess the 10-year risk of recurrence in an untreated population that was not selected for ER/HER2 results. The Oncotype DX® Recurrence Score® (RS, Genomic Health, Inc.) is a 21-gene RT-PCR assay that is clinically validated to predict the 10-year risk of distant recurrence in ER+ patients treated with Tamoxifen. MammoStrat® (MS, Clarient, Inc.) is an IHC assay that uses 5 antibodies and has been validated in a similar population as RS. Several recent reports show that these assays classify patients differently with significant discordances for all risk groups (Shivers, et al., SABCS 2013; Denduluri, et al., ASCO Breast 2011; Poulet, et al., SABCS 2012; Schneider, et al., ASCO 2013). The present study is an analysis of long-term follow-up in a cohort of patients who have results for all three of these risk-stratifying assays side by side in the same samples. Methods: Patients with ER+ N0-N1 early-stage breast cancer with an MP result obtained as part of their routine clinical care were identified at the University of South Florida (USF, N=65) and Morton Plant Hospital (N=83). After local IRB approval, slides and/or blocks were cut and de-identified at USF and sent to Genomic Health and Clarient for blinded testing. Clinicopathological features were also reviewed by 3 breast pathologists. Results: 148 patients with an MP result had tissue available to send for RS and MS assays. These patients had a median age of 62 years; median tumor size 1.8 cm; 9% low grade, 59% intermediate grade and 32% high grade. In our previous analysis of this study, of 148 patients with MP results, 53% were low risk and 47% were high risk. Of 135 samples that yielded enough RNA to produce an RS result, 53% were low risk, 26% were intermediate risk and 21% were high risk. Of 129 samples that yielded an MS result, 44% were low risk, 28% were moderate risk and 28% were high risk. Of 121 patients with results for all 3 assays, only 22% were concordant for low risk and 9% were concordant for high risk across all 3 assays. Overall, 30% of cases showed a major discordance such as low risk for one assay and high risk for another. After median follow-up of 54 months, 9 patients have had a distant metastasis and/or 8 patients have died (11 patients total). One patient who had bone metastasis and died had been classified as low risk by all 3 assays. Three patients with distant metastases had a major discordance between assays, with two high risk and one low risk result. Seven patients were classified as high or intermediate/moderate risk by all 3 assays. Conclusions: This direct comparison demonstrates that although the assays classify a large proportion of patients differently, the patients who ended up with a distant metastasis and/or died of breast cancer had been classified as high risk by at least two of the three assays. This study has important clinical implications since these assays are used to help make treatment decisions regarding which patients might benefit from chemotherapy. Citation Format: Shivers SC, Russell S, Blumencrancz L, Mehindru A, Acs G, Ellis D, Vrcelj V, Zanchi A, Blumencrancz PW, Carter E, King J, Cox CE. Long-term follow-up of early stage breast cancer patients with results of MammaPrint®, Oncotype DX® and MammoStrat® risk classification assays [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-45.

Abstract P3-13-08: A prospective, single-arm, multi-site, clinical evaluation of the SAVI SCOUT® surgical guidance system for the location of non-palpable breast lesions during excision

Background and Objectives: The standard preoperative technique for localizing non-palpable breast lesions is wire localization (WL). Radioactive seed localization (RSL) is an alternative approach that addresses a number of clear disadvantages associated with WL but, the adoption of RSL has been impacted by considerable regulatory requirements for the handling of radioactive materials. To advance the progress made with RSL and eliminate issues associated with radioactive components, the SAVI SCOUT® surgical guidance system was developed. SAVI SCOUT is an FDA-cleared medical device that utilizes non-radioactive electromagnetic wave technology to provide real-time guidance during excisional breast procedures. The purpose of this study is to evaluate the performance of SAVI SCOUT in guiding the removal of non-palpable breast lesions. Methods: Following a 50 patient pilot study that showed SAVI SCOUT to be safe and effective, IRB approval was granted for this prospective, single-arm, multi-site study for women with a non-palpable breast lesion. Pts underwent localization and excision with the SAVI SCOUT system, which consists of an electromagnetic wave reflective device (reflector), handpiece and console. Using mammographic or ultrasound guidance, the reflector was implanted into the target tissue. Before making an incision, the surgeon used the handpiece, which emits electromagnetic waves and infrared light, to detect the location of the reflector and subsequently plan the surgical incision. During the procedure, the surgeon used the handpiece to guide the localization and removal of the reflector along with the surrounding breast tissue. The console provides audible feedback of reflector proximity to the handpiece. Successful reflector placement, localization and retrieval were the primary endpoints. Results: A total of 61 pts have participated in the study to date, along with 7 surgeons and 9 radiologists across 6 institutions. The reflectors were successfully placed in all pts, including 27 under mammographic guidance and 34 under ultrasound guidance. In 28 cases, the reflectors were placed on the same day as surgery. Otherwise, the reflectors were placed up to 7 days (average 2.9 days) before surgery. Thirteen pts underwent excisional biopsy and 48 pts had a lumpectomy. The intended lesion and reflector were successfully removed in all pts. Reflector migration did not occur and no adverse events occurred. Final pathology is currently available for 52 pts: 8/10 excisional biopsy pts had no invasive or in situ carcinoma identified. For pts with cancer and complete data, 39/39 had clear margins, but one patient was recommended for re-excision due to a close margin (1 mm) for DCIS. Conclusions: The preliminary data from this prospective, multi-site study show that real-time surgical guidance with SAVI SCOUT is an accurate technique for directing the removal of non-palpable breast lesions and is reproducible at multiple clinical sites. At present, the study has yielded 100% surgical success with a re-excision rate of 3.0%. Ongoing accrual to this clinical evaluation study will validate these findings with planned enrollment of 150 pts at up to 15 total sites. Citation Format: Cox CE, Prati R, Blumencranz P, Allen K, Banull C, Cline M, Howard T, Portillo M, Whitworth P, Funk K, Police A, Lin E, Combs F, Anglin B, King J, Shivers SC. A prospective, single-arm, multi-site, clinical evaluation of the SAVI SCOUT® surgical guidance system for the location of non-palpable breast lesions during excision. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-13-08.

Abstract P1-16-10: Pilot study of a passive non-radioactive electromagnetic wave technology to localize non-palpable breast lesions

Background and Objectives: The standard preoperative technique for localizing non-palpable breast lesions is wire localization (WL). Radioactive seed localization (RSL) has been described as an alternative approach to address the number of clear disadvantages associated with WL. Yet, despite its proven advantages, the adoption of RSL has been impacted by considerable regulatory requirements for the handling of radioactive materials. To advance the progress made with RSL and eliminate the issues associated with radioactive components, the SAVI Scout® surgical guidance system has been developed. The SAVI Scout surgical guidance system is an FDA-cleared medical device that utilizes passive non-radioactive electromagnetic wave technology to provide real-time guidance during excisional breast procedures. The purpose of this pilot study is to determine the safety and efficacy of the SAVI Scout system in localizing and directing the removal of non-palpable breast lesions during excisional biopsy and lumpectomy procedures. The preliminary results from two institutions are reported. Materials and Methods: Following a feasibility study using the SAVI Scout system in resected breast tissues ex vivo , Institutional Review Board approval was granted for both institutions for women with a non-palpable breast lesion requiring preoperative localization for excision. Participating patients underwent localization and excision with the SAVI Scout system, which consists of an electromagnetic wave reflective device (reflector), handpiece and console. Using mammographic or ultrasound guidance, the reflector was placed percutaneously up to 7 days prior to the scheduled excisional procedure. At surgical excision, the surgeon used the SAVI Scout handpiece to locate the reflector, which was removed along with the surrounding breast tissue. The console provides audible feedback of reflector proximity to the handpiece. Successful reflector placement, localization and retrieval were the primary endpoints. Results: After the first training case (data not used), a total of 17 patients have participated in the study to date. The reflectors were successfully placed with mammographic guidance in 9/9 patients and with ultrasound guidance in 8/8 patients. Reflectors were placed an average of 1.7 days (range 0-6 days) before surgery. Five patients underwent excisional biopsy and 12 patients had a lumpectomy. The intended lesion and reflector were successfully removed in 17/17 patients. Reflector migration did not occur and no adverse events occurred. Of the 14 patients in which final pathology is currently available, 6 patients had no invasive or in situ carcinoma identified, 4 had no tumor in the excision, and 3/4 patients with tumor had clear margins. One patient had a focally positive margin and was recommended for re-excision. Conclusions: The preliminary data show the SAVI Scout system to be a safe and effective tool for the localization of non-palpable breast lesions. Ongoing accrual to this pilot study will validate these findings with planned enrollment of a total of additional 50 patients in the next 60 days at up to 3 additional sites. Citation Format: Charles E Cox, Melissa Themar-Geck, Ronald Prati, Michelle Jung, Jeff King, Steven C Shivers. Pilot study of a passive non-radioactive electromagnetic wave technology to localize non-palpable breast lesions [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-16-10.