Oncologic Safety of Staged Prepectoral Implant Reconstruction following Nipple-Sparing Mastectomy: A Mean 9-Year Follow-Up.

BACKGROUND: Prepectoral reconstruction following nipple-sparing mastectomy has recently gained popularity as an alternative to total or partial submuscular reconstruction. In the absence of long-term follow-up, concerns have been raised over the oncologic safety of using mastectomy flaps that preserve the entire thickness of the subcutaneous fat and its circulation. In this article, the authors present their average 9-year oncologic follow-up of patients who underwent nipple-sparing mastectomy and two-stage prepectoral implant reconstruction without acellular dermal matrix. METHODS: In this retrospective study, a group of previously reported (151 consecutive) breast cancer patients [246 breasts (160 therapeutic and 86 preventative)] who underwent nipple-sparing mastectomy and staged prepectoral implant reconstruction between 2005 and 2015 were followed up for an average of 109 months (range, 14 to 192 months). Tumor-related data, oncologic markers, staging, neoadjuvant/adjuvant therapy, and radiation therapy were evaluated to determine local recurrence, overall survival, and disease-free survival rates. RESULTS: The local recurrence rate in 151 patients was 2.6 percent. Eleven patients (7.3 percent) died as a result of metastatic disease and three patients died as a result of unrelated causes. The average 109-month overall survival rate was 92.9 percent, and the disease-free survival rate was 87.8 percent. Over the same period, nine patients (6 percent) were alive with distant disease. CONCLUSION: The authors' 9-year two-stage prepectoral reconstruction study of nipple-sparing mastectomy shows that the procedure is oncologically safe, having comparable recurrence, overall survival, and disease-free survival rates as total mastectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Recurrence rates for patients with early-stage breast cancer treated with IOERT at a community hospital per the ASTRO consensus statement for APBI.

PURPOSE: To report the recurrence rates after single-fraction intraoperative electron radiotherapy (IOERT) in patients with early-stage breast cancer treated on a single institution prospective Phase I/II protocol at a community hospital. Results were retrospectively analyzed according to suitability criteria from the updated American Society for Radiation Oncology (ASTRO) consensus statement for accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: Patients over 40 years with early-stage invasive or in situ breast cancer (<2.5 cm and node negative) were enrolled. IOERT 2100 cGy was delivered during breast conservation surgery, and patients were followed up for a median of 3 years (0.8-6.5 years) to determine toxicity and recurrence rates. RESULTS: Single-fraction IOERT was performed in 215 cases (6 bilateral treatments, 196 patients) with 13 patients receiving whole-breast radiation (WBR) after IOERT for adverse pathologic features. Of 202 cases of IOERT without WBR, 89 patients experienced an ipsilateral breast tumor recurrence (IBTR) giving a cumulative incidence of 3.96%. When the ASTRO APBI suitability criteria were applied, the IBTR rate was significantly lower for suitable patients vs. cautionary or unsuitable patients (1.6% vs. 3.4% vs. 21.0%, p = 0.0002). 3-year progression-free survival after IOERT alone was 93.4%. For patients who received standard WBR (4500-5040 cGy) after IOERT, no Grade 3 or 4 toxicities (acute or late) occurred and all patients are disease-free. CONCLUSIONS: Single-fraction IOERT results in a low rate of IBTR when strictly adhering to ASTRO criteria for APBI suitability. Standard dose WBR for unfavorable pathologic results after 2100 cGy IOERT is well tolerated.

Secondary Mastopexy After Nipple-Sparing Mastectomy and Staged Subcutaneous Expander/Implant Reconstruction.

BACKGROUND: The acceptance of nipple-sparing mastectomy for the treatment of breast cancer in selected patients has introduced ancillary procedures to improve breast shape, correct ptosis, and enhance breast symmetry. Mastopexy before or at the time of nipple-sparing mastectomy has been performed to correct ptosis, but there have been no reports on secondary Wise pattern mastopexy after completion of staged subcutaneous expander/implant reconstruction. METHODS: Between 2005 and 2015, 155 patients (255 breasts) underwent staged subcutaneous implant/expander-based reconstruction after inframammary nipple-sparing mastectomy. Of the 155 patients, 10 (6.5%) patients required a secondary Wise pattern mastopexy (n = 14, 5.5%). The nipple was raised 2.5 to 6 cm (range, 3.8 cm), and the implant location was adjusted accordingly for optimal positioning with respect to the nipple-areola. The secondary mastopexy was performed to correct ptosis, improve breast symmetry and/or contour deformities of the breast, and relieve pain associated with large implants. RESULTS: All mastopexies healed without complications, and the goals of the revisions were achieved. There were no capsular contractures after an average of 50 months (range, 19-92 months). The patients were satisfied with the aesthetic and functional improvement. CONCLUSIONS: Secondary mastopexy after 2-stage subcutaneous expander/implant breast reconstruction is uncommon, but if needed, it may be safely performed to correct ptosis and improve breast shape, symmetry, and function.

Meta-Analysis of Local Invasive Breast Cancer Recurrence After Electron Intraoperative Radiotherapy.

BACKGROUND: Electron intraoperative radiotherapy (IORT) can be used during breast conserving surgery to treat early-stage invasive breast cancer. Using data from current clinical and observational studies, this study aimed to assess the impact of single-fraction electron IORT on local recurrence rates. METHODS: Studies on single-fraction electron IORT during breast conserving surgery were identified through a search of PubMed and Google Scholar, as well as through secondary referencing. Local recurrence rate was the main outcome of interest. A meta-analysis of proportions using a binomial distribution to model the within-study variability and a random effects model was conducted to estimate a pooled local recurrence rate. To estimate a 5-year recurrence rate, a single-sample Poisson-normal model was applied to model the probability of events occurring during a fixed period (60 months). RESULTS: The study identified 13 publications. The analysis demonstrated a pooled monthly local recurrence rate of 0.02% per person-month (95% confidence interval CI 0.00-0.06%) for the studies with a follow-up period shorter than 5 years, 0.03% per person-month (95% CI 0.02-0.06%) for studies with a follow-up period of 5 years or longer, and 0.02% per person-month (95% CI 0.01-0.04%) overall. Based on this model, the predicted 5-year local recurrence rate was 2.7% (range 1.9-3.7%). CONCLUSIONS: According to the published literature, the rate of breast cancer local recurrence after electron IORT was 0.02% per person-month, with an adjusted 5-year recurrence rate of 2.7%. These findings support the recent guidelines from the American Society for Radiation Oncology (ASTRO) supporting the use of electron IORT for low-risk patients.

Staged Suprapectoral Expander/Implant Reconstruction without Acellular Dermal Matrix following Nipple-Sparing Mastectomy.

BACKGROUND: Since the introduction of nipple-sparing mastectomy as an oncologically safe procedure for the treatment of breast cancer, reconstructive efforts for immediate staged expander/implant reconstruction have focused on submuscular implantation with or without acellular dermal matrix. Suprapectoral reconstruction without acellular dermal matrix has received little attention in the reconstructive literature of nipple-sparing mastectomy. METHODS: Between 2005 and 2015, 155 patients (250 breasts) underwent nipple-sparing mastectomy with prepectoral staged expander/implant reconstruction using thick mastectomy skin flaps without acellular dermal matrix. Patients with different breast sizes, including those patients with very large breasts who required a primary mastopexy, were considered candidates for the suprapectoral reconstruction. Tumor-related data, comorbidities, and preoperative or postoperative radiation therapy were evaluated for correlation with the final outcome. RESULTS: Patients were followed up for an average of 55.5 months (range, 138.1 to 23.6 months). The tumor recurrence rate was 2.6 percent. Adverse outcomes such as capsular contracture, implant dystopia, and rippling were studied. Aesthetic outcome, based on a three-point evaluation scale, showed 53.6 percent of patients as having a very good result, 31.6 percent showing a good result, 9 percent showing a fair result, and 5.8 percent showing a poor result. CONCLUSIONS: The suprapectoral two-stage expander/implant reconstruction without acellular dermal matrix in nipple-sparing mastectomy has certain advantages with respect to breast shape, less morbidity related to expansion, ease of reconstruction, and cost effectiveness. These advantages have to be weighed against those of subpectoral reconstruction with acellular dermal matrix to determine the method of choice. CLINCAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Linguistic validation of the Spanish version of the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

PURPOSE: The U.S. NCI's PRO-CTCAE is a library of self-report items for assessing symptomatic adverse events in cancer clinical trials from the patient perspective. The aim of this study was to translate and linguistically validate a Spanish version. METHODS: PRO-CTCAE's 124 items were translated from English into Spanish using multiple forward and back translations. Native Spanish speakers undergoing cancer treatment were enrolled at six cancer treatment sites. Participants each completed approximately 50 items and were then interviewed using cognitive probes. The interviews were analyzed at the item level by linguistic themes, and responses were examined for evidence of equivalence to English. Items for which ≥20 % of participants experienced difficulties were reviewed, and phrasing was revised and then retested in subsequent interviews. Items where <20 % of respondents experienced difficulties were also reviewed and were considered for rephrasing and retesting. RESULTS: One hundred nine participants from diverse Spanish-speaking countries were enrolled (77 in Round 1 and 32 in Round 2). A majority of items were well comprehended in Round 1. Two items presented difficulties in ≥20 % of participants and were revised/retested without further difficulties. Two items presented difficulties in <20 %, and when retested exhibited no further difficulties. Two items presented difficulties in <20 %, but were not revised due to lack of alternatives. Sixteen items presented difficulties in ≤12 % and were not revised because difficulties were minor. CONCLUSIONS: The Spanish PRO-CTCAE has been developed and refined for use in Spanish-speaking populations, with high levels of comprehension and equivalence to the English PRO-CTCAE. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01436240.

Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

BACKGROUND: PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. METHODS: Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0-4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. RESULTS: 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55-0.90); tablet vs paper: 0.81 (0.62-0.96); IVRS vs paper: 0.78 (0.60-0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = -0.04 [-0.16-0.22]; tablet vs paper = -0.02 [-0.11-0.14]; IVRS vs paper = 0.02 [-0.07-0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/-0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported "no problems" responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. CONCLUSIONS: Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. TRIAL REGISTRATION: NCT Clinicaltrials.gov identifier: NCT02158637.

Primary Buttonhole Mastopexy and Nipple-Sparing Mastectomy: A Preliminary Report.

BACKGROUND: Patients undergoing nipple-sparing mastectomy and immediate-implant based reconstruction occasionally require a mastopexy based on their breast size and degree of ptosis. Previous reports have shown the feasibility of mastopexy-nipple-sparing mastectomy in selected patients to raise the nipple up to 5 cm. Major mastopexy with nipple transposition more than 6 cm in conjunction with nipple-sparing mastectomy for therapeutic indications has not been described. The authors review their experience with primary buttonhole mastopexy performed in conjunction with nipple-sparing mastectomy. METHODS: Between 2008 and 2014, 16 patients (32 breasts) underwent bilateral primary mastopexy and nipple-sparing mastectomy with immediate staged implant-based reconstruction. The Passot buttonhole technique was used for the mastopexy in all patients, raising the nipple from 7 to 12 cm. Tumor-related data, risk factors, breast size, degree of ptosis, expander size, fill volume, selection criteria, and complications are discussed. RESULTS: The average follow-up period was 33 months (range, 14 to 80 months). There were no tumor recurrences, and all patients completed their reconstruction. Two patients required removal of the expander and delayed reconstruction because of infection and implant exposure due to nipple-areola loss. The reasons for nipple-areola loss and technical modifications to enhance skin viability by retaining a thin layer of subareolar breast tissue for removal during the second-stage implant exchange are discussed. CONCLUSIONS: Primary mastopexy using the buttonhole technique performed together with nipple-sparing mastectomy is a safe procedure with predictable results in patients with very large or ptotic breasts requiring lifts greater than 6 cm. The success of the combined procedure depends on preserving a thin layer of subareolar breast tissue and removing it at the time of implant exchange.

Validity and Reliability of the US National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

IMPORTANCE: To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). OBJECTIVE: To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items. DESIGN, SETTING, AND PARTICIPANTS: A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit. MAIN OUTCOMES AND MEASURES: Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30). RESULTS: A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO-CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P<.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P<.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median [range] intraclass correlation coefficient, 0.76 [0.53-.96]). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes were statistically significant for 27 prespecified items (median [range] r=0.43 [0.10-.56]; all P≤.006). CONCLUSIONS AND RELEVANCE: Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous US sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are under way to inform further development of PRO-CTCAE and its inclusion in cancer trials.

Margins: a status report from the Annual Meeting of the American Society of Breast Surgeons.

Since the emergence of breast conserving surgery (BCS) as an alternative to mastectomy in the 1980's, there has been little consensus on what constitutes acceptable margins for cases of invasive breast cancer, how best to evaluate margins in the operating room, or an understanding of the challenging process of margin assessment by pathologists. The program committee for the 15th Annual Meeting of The American Society of Breast Surgeons organized a plenary session to discuss the latest thinking and guidelines for these important issues. The SSO/ASTRO Consensus Guideline on Margins for BCS was an important focus of discussion. The SSO/ASTRO consensus panelists concluded that "no ink on tumor" is an adequate surgical margin for BCS in patients with invasive breast cancers. Intraoperative strategies to decrease the incidence of positive margins include intraoperative localization techniques (wire-localization, ultrasound, radioactive seed) and intraoperative margin assessments with specimen radiography, imprint cytology, and frozen section. Studies also demonstrate the positive effect of shave margins with or without intraoperative margin assessment. The College of American Pathologists protocols for breast specimen margin evaluation consider multiple variables that can impact the proper assessment of margins. These variables include: tissue fixation time, specimen orientation, cold ischemia time, leaking ink, specimen pancaking and others that surgeons need to be aware of. Determining when "enough is enough" should not only be the application of guidelines and national standards, but also a multidisciplinary discussion between breast cancer specialists for what is right for the individual patient's unique circumstances.

Inframammary approach to nipple-areola-sparing mastectomy.

BACKGROUND: Different approaches have been advocated for performing nipple-areola-sparing mastectomy. The inframammary approach has been viewed as having limited applications, particularly in large breasts. The authors review their experience with nipple-areola-sparing mastectomy using the inframammary approach for different breast sizes. METHODS: Between 2005 and 2012, 118 nipple-areola-sparing mastectomies with staged implant-based reconstruction were performed in 80 consecutive patients. Patients with different breast sizes underwent inframammary nipple-areola-sparing mastectomy, except those patients who had very large breasts or those who requested a breast lift. Oncologic data related to tumor size, selection criteria, and recurrences are presented. All nipple-areola-sparing mastectomies and reconstructions were performed by the same surgeons (J.K.H. and A.H.S), who operated as a team in performing the mastectomies. RESULTS: Patients were followed up from 6 to 97 months (mean, 33.5 months). There were four recurrences (5 percent), three of which were attributed to the biological behavior of the tumor. The aesthetic outcomes of the reconstructions were analyzed based on nipple location, breast contour, and symmetry: 35 patients (44 percent) had a very good result, 28 (35 percent) had a good result, nine (11 percent) had a fair result, and eight (10 percent) had a poor result. Risk factors and complications affecting the final aesthetic outcome are discussed. CONCLUSIONS: The inframammary approach for nipple-areola-sparing mastectomy is the authors' procedure of choice for small, medium, and large breasts. The team approach to the mastectomy facilitates the procedure, reduces skin-related complications, and results in a better aesthetic outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Intraoperative electron radiotherapy boost as a component of adjuvant radiation for breast cancer in the community setting.

To reduce toxicity/treatment time and improve accuracy, intraoperative electron radiotherapy (IOERT) was used as an alternative to electron beam radiation therapy boost. Primary objective was to determine feasibility and acute toxicity. From August 2009 to June 2011, 50 patients (age 32 to 76 years) with in situ or invasive breast cancer (Stage 0 to IIIA) were treated. Toxicity assessed according to standard National Cancer Institute scales. Median tumor size was 20 mm (range, 6 to 80 mm) with 43 infiltrating ductal, two infiltrating lobular, and five ductal in situ carcinoma. A single 10-Gy fraction boost was given to the tumor bed after resection followed by whole-breast radiotherapy. After IOERT, three patients required completion axillary lymph node dissection, eight had reexcision resulting from positive margins, and four opted for completion mastectomy. The median follow-up was 10 months (range, 2 to 24 months). Ten patients had Grade 1 and one reported Grade 2 breast pain 2 weeks after IOERT; all resolved at 6 weeks. Two patients had delay in wound healing, but none developed a wound infection. Three patients reported symptomatic fat necrosis. No other toxicities were reported. IOERT resulted in a reduction in treatment time, was not associated with additional toxicity or change in the acute toxicity profile, and is a feasible treatment option in a community hospital setting.

The role of the breast cancer surgeon in personalized cancer care: clinical utility of the 21-gene assay.

BACKGROUND: Breast cancer surgeons represent the first line of defense for many patients battling this disease. They often have the first contact to discuss treatment options with the patient after diagnosis. However, the potential impact of this consultation has evolved with the arrival of commercialized multigene prognostic and predictive tests that continue to reshape the landscape of breast cancer management, including modern surgical practice. METHOD: This review was compiled from peer-reviewed literature indexed in PubMed. CONCLUSIONS: The advent of genomic analysis has advanced the treatment and management of breast cancer toward the goal of personalized care. Therefore, the role of the surgeon now extends beyond extirpation of the tumor and includes an understanding of the biology of the disease as well as an appreciation of this new technology. Breast cancer surgeons should seize this opportunity to provide patients and colleagues with this information in an expeditious manner to optimize clinical outcomes.

Breast cancer management in low resource countries (LRCs): consensus statement from the Breast Health Global Initiative.

The Breast Health Global Initiative (BHGI) brought together international breast cancer experts to discuss breast cancer in low resource countries (LRCs) and identify common concerns reviewed in this consensus statement. There continues to be a lack of public and health care professionals' awareness of the importance of early detection of breast cancer. Mastectomy continues to be the most common treatment for breast cancer; and a lack of surgeons and anesthesia services was identified as a contributing factor in delayed surgical therapy in LRCs. Where available, radiation therapy is still more likely to be used for palliation rather than for curative treatment. Tumor receptor status is often suboptimally performed due to lack of advanced pathology services and variable quality control of tissue handling and processing. Regional pathology services can be a cost-effective approach and can serve as reference, training and research centers. Limited availability of medical oncologists in LRCs often results in non-specialist providing chemotherapeutic services, which requires additional supervision and training. Palliative care is an emerging field in LRCs that requires investment in training and infrastructure development. A commitment and investment in the development of breast cancer care services by LRC governments and health authorities remains a critical need in LRCs.

Areola and nipple-areola-sparing mastectomy for breast cancer treatment and risk reduction: report of an initial experience in a community hospital setting.

BACKGROUND: The use of areola-sparing (AS) or nipple-areola-sparing (NAS) mastectomy for the treatment or risk reduction of breast cancer has been the subject of increasing dialogue in the surgical literature over the past decade. We report the initial experience of a large community hospital with AS and NAS mastectomies for both breast cancer treatment and risk reduction. METHODS: A retrospective chart review was performed of patients undergoing either AS or NAS mastectomies from November 2004 through September 2009. Data collected included patient sex, age, family history, cancer type and stage, operative surgical details, complications, adjuvant therapies, and follow-up. RESULTS: Forty-three patients underwent 60 AS and NAS mastectomies. Forty-two patients were female and one was male. The average age was 48.7 years (range, 28-76 years). Forty mastectomies were for breast cancer treatment, and 20 were prophylactic mastectomies. The types of cancers treated were as follows: invasive ductal (n = 19), invasive lobular (n = 5), ductal carcinoma-in situ (n = 15), and malignant phyllodes (n = 1). Forty-seven mastectomies (78.3%) were performed by inframammary incisions. All patients underwent immediate reconstruction with either tissue expanders or permanent implants. There was a 5.0% incidence of full-thickness skin, areola, or nipple tissue loss. The average follow-up of the series was 18.5 months (range, 6-62 months). One patient developed Paget's disease of the areola 34 months after an AS mastectomy (recurrence rate, 2.3%). There were no other instances of local recurrence. CONCLUSIONS: AS and NAS mastectomies can be safely performed in the community hospital setting with low complication rates and good short-term results.

Focused microwave thermotherapy for preoperative treatment of invasive breast cancer: a review of clinical studies.

BACKGROUND: Preoperative focused microwave thermotherapy (FMT) is a promising method for targeted treatment of breast cancer cells. Results of four multi-institutional clinical studies of preoperative FMT for treating invasive carcinomas in the intact breast are reviewed. METHODS: Externally applied wide-field adaptive phased-array FMT has been investigated both as a preoperative heat-alone ablation treatment and as a combination treatment with preoperative anthracycline-based chemotherapy for breast tumors ranging in ultrasound-measured size from 0.8 to 7.8 cm. RESULTS: In phase I, eight of ten (80%) patients receiving a single low dose of FMT prior to receiving mastectomy had a partial tumor response quantified by either ultrasound measurements of tumor volume reduction or by pathologic cell kill. In phase II, the FMT thermal dose was increased to establish a threshold dose to induce 100% pathologic tumor cell kill for invasive carcinomas prior to breast-conserving surgery (BCS). In a randomized study for patients with early-stage invasive breast cancer, of those patients receiving preoperative FMT at ablative temperatures, 0 of 34 (0%) patients had positive tumor margins, whereas positive margins occurred in 4 of 41 (9.8%) of patients receiving BCS alone (P = 0.13). In a randomized study for patients with large tumors, based on ultrasound measurements the median tumor volume reduction was 88.4% (n = 14) for patients receiving FMT and neoadjuvant chemotherapy, compared with 58.8% (n = 10) reduction in the neoadjuvant chemotherapy-alone arm (P = 0.048). CONCLUSIONS: Wide-field adaptive phased-array FMT can be safely administered in a preoperative setting, and data from randomized studies suggest both a reduction in positive tumor margins as a heat-alone treatment for early-stage breast cancer and a reduction in tumor volume when used in combination with anthracycline-based chemotherapy for patients with large breast cancer tumors. Larger randomized studies are required to verify these conclusions.