Candidates For Breast-conserving Therapy Research Articles

Abstract P2-15-08: Aesthetic Incisions and Early Complications for Nipple-sparing Mastectomy followed by Immediate Breast Reconstruction

Abstract Introduction: Nipple-sparing mastectomy (NSM) is a surgical alternative for patients who are not candidates for breast-conserving therapy in early breast cancer or even for women who are candidates for risk-reducing mastectomies, facilitating immediate breast reconstruction. Aesthetic incisions such as through the inframammary fold (IMF) or periareolar (PA) are viable options for radial scars, with better cosmetic results and less visibility. Little is known about early surgical complications between these two techniques. Objectives and methods The aim of this study was to evaluate early complications (NAC necrosis [mild, partial or total], infection, seroma, hematoma, dehiscence and reconstruction failure) in patients undergoing NSM via esthetic incisions (IMF or PA) and immediate breast reconstruction in a unique Brazilian institution. A retrospective analysis was performed at Hospital Geral de Fortaleza (HGF) between 2015 and 2022, including patients with a minimum follow-up of 3 months and complete data in the medical records. The following demographic parameters were evaluated: age, body mass index, co-morbidities, use of direct implant or tissue expander, breast weight and pre-pectoral or submuscular reconstruction. Pearsons chi squared tests and t-test were performed and a p value of < 0.05 was considered statistically significant. Results A total of 180 NSM through IMF (n=106) or PA (n=74) incisions were included and 43 cases (23.9%) of complications were observed: 27 in the PA group (62.8%) and 16 in the IMF (37.2%), with this difference being significant (p=0.0002). Regarding NAC necrosis, 65.4% were observed in the PA incision (n=17; 22.4%), compared to 34.6% in the IMF (n=9; 8.7%) (p=0.0023). There was no significant difference in relation to other complications (n=7 [IMF] vs n=10 [PA]), just as there was no difference in relation to the demographic parameters evaluated, except for the pre-pectoral and direct-to-implant reconstruction, which were more frequently performed in the IMF group: 19 (18.3%) vs 3 (4%) and 52 (50%) vs 24 (31.6%) cases respectively. Only 2 patients had breast reconstruction failure, both in the PA cohort. Conclusions Both incisions are viable options for accessing the NSM, with an acceptable rate of complications. The PA incision is related to a higher complication rate compared to IMF, based mainly on the NAC necrosis rate. More studies are needed for a better understanding of this scenario. Citation Format: Francisco Pimentel Cavalcante, Guilherme Novita, Ticiane Oliveira Lima, Ryane Alcantara, Amanda Cardoso, Flora Ulisses, Felipe Zerwes, Eduardo Millen. Aesthetic Incisions and Early Complications for Nipple-sparing Mastectomy followed by Immediate Breast Reconstruction [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-15-08.

Choice of Mastectomy May Increase the Extent of Axillary Surgery in Women with Breast Cancer

Based on the ACOSOG Z0011 trial, women who undergo breast conservation therapy (BCT) and have limited disease in the axilla on sentinel lymph node (SLN) biopsy do not require axillary lymph node dissection (ALND). In this study we investigate the incidence of ALND in patients undergoing elective mastectomy with limited disease in the axilla to identify how many women may have been spared additional axillary surgery if they chose BCT. All women with invasive breast cancer treated at a single tertiary care breast center from 2010-2018 who were candidates for BCT but elected mastectomy and underwent SLN biopsy were identified through retrospective review of a prospectively maintained database. The primary outcome of interest was the incidence of ALND in women found to have a limited burden of disease in the axilla (1-2 positive SLNs). The study population comprised 151 patients with invasive breast cancer eligible for BCT who chose mastectomy. On final pathology, 34 patients had 1-2 positive SLNs, and 16 of these patients underwent completion ALND. These 16 patients out of 151 overall lumpectomy candidates electing mastectomy (10.6%) could have been spared ALND if they did not elect mastectomy. BCT candidates electing mastectomy have a 10.6% chance of undergoing more extensive axillary surgery than would have been recommended with BCT alone. The increased risk of undergoing additional axillary surgery should be incorporated into the preoperative discussion for patients choosing between BCT and mastectomy.

Choosing Between Mastectomy and Breast-Conserving Therapy: Is Patient Distress an Influencing Factor?

Breast-conserving therapy (BCT) offers oncologic outcomes similar to those of mastectomy, yet many patients, when provided the option, choose mastectomy. This study aimed to evaluate the relationship between patient-reported distress and surgical decisions and to determine factors predictive of choosing BCT versus mastectomy. Patients with newly diagnosed breast cancer deemed candidates for BCT who completed a distress screen at their initial visit to an academic institution between 2016 and 2019 were retrospectively reviewed. This screening tool captures distress in emotional, social, health, and practical domains on a scale of 0 to 10. The distress scores were compared against surgical decisions using nonparametric Wilcoxon rank-sum tests. Patient factors associated with surgical choice were analyzed using chi-square, Fisher's exact, and Student's t tests. A two-sided p value lower than 0.05 was considered significant. Of 506 patients deemed eligible for BCT, 430 (85%) chose BCT and 76 (15%) pursued mastectomy. The distress levels did not differ significantly between the surgical options. The patients who underwent mastectomy were on the average younger (50.7 vs 60.4 years; p < 0.0001), presented with palpable masses (p < 0.0001), had stage 0, 2, or 3 versus stage 1 disease (p < 0.0001), sought consultation for second opinions (19.7% vs 8.6%; p = 0.0032), received neoadjuvant chemotherapy (31.6% vs 16.3%; p = 0.0016), or had deleterious gene mutations (21.1% vs 5.1%; p < 0.0001). Distress was not associated with the pursuit of surgical treatment. Rather, younger age, search for a second opinion, and a palpable mass present at presentation were associated with more aggressive surgical decisions. Understanding factors that influence surgical decision-making is critical in guiding informed decisions that reflect patient values.

Abstract PS1-17: Comparing survival differences between breast-conserving therapy and mastectomy in patients with early-stage breast cancer undergoing upfront surgery

Abstract Background: Over the last decade, patients with early-stage breast cancer have been undergoing total mastectomy (TM) with increasing frequency. Our center reported that local recurrence rates with breast conserving therapy (BCT) declined throughout the 27-year period: from 7.1% for patients treated during 1970–1984 to 1.3% for patients treated during 1994–1996. More recently, several groups have published slightly improved survival rates in patients undergoing BCT compared with TM. The aim of this study was to evaluate trends in TM rates and compare overall survival (OS), distant metastasis-free survival (DMFS), local-regional recurrence (LRR) and disease-specific survival (DSS) between BCT and TM in patients with early-stage breast cancer undergoing upfront surgery. Methods: We identified women with clinical stage T1–2, N0–1, M0 breast cancer who underwent surgery as first treatment modality from 1/1/2000 to 12/31/2014 at our center. TM rates and survival outcomes were evaluated. Because the decision for surgery for those patients was not random, differences in patient, tumor and treatment characteristics with respect to surgery types were adjusted using inverse probability weighting (IPW) based on propensity scores. Variables in the model included age at diagnosis, clinical tumor T category, clinical nodal category, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) status and year of surgery, and a multinomial logit model was used for surgery treatment assignment and a Gamma model was used for the time to censor. IPW models were used to adjust for impact of surgery types on survival outcomes. Similar analysis was used in 6 subsets: Stage I &amp; hormone receptor (HR)+/HER2-, Stage I &amp; HER2+, Stage I &amp;triple negative breast cancer (TNBC), Stage II &amp; HR+/HER2-, Stage II &amp; HER2+, Stage II &amp; TNBC. Patients undergoing TM with RT were excluded from subset analysis due to small sample size. Results: A total of 8,256 patients were included, of them, 4701 (56.9%) underwent BCT, 2862 (34.7%) underwent TM without RT and 693 (8.4%) underwent TM+RT. Patients who underwent TM were younger and were more likely to have larger tumors, positive lymph nodes, higher grade, and HER2-positive tumors. TM rates increased in patients &amp;lt;=50 years old from 2006-2013. At a median follow-up time of 6.1 years, multivariable Cox model showed that patients who underwent BCT had improved OS (HR: 0.8,95%CI: 0.7-0.99, P=0.02) and had a similar DSS, DMFS, and LRR compared to patients who underwent TM without RT. After IPW adjusting, patients undergoing BCT had a slightly worse DSS (RR: 1.2, 95%CI: 1.02-1.4, P=0.03) and similar OS, DMFS and LRR compared to patients underwent TM without RT in the whole cohort. In subset analyses, after IPW adjusting, there were no survival differences in OS, DSS, and DMFS between TM without RT and BCT. Patients with TNBC undergoing BCT had a lower LRR compared to TM (RR: 0.4, 95% CI: 0.3-0.6, P&amp;lt;0.001) regardless of clinical stage. Conclusions: In whole cohort, after IPW adjusting, patients undergoing BCT had a slightly worse DSS compared to patients underwent TM without RT, and those differences in DSS have disappeared in the subset analysis. LRR was lower in patients with TNBC breast cancer undergoing BCT although there as a similar OS, DSS and DMFS compared with TM in subset analysis. These contemporary data may help physicians in surgical decision making for patients who are candidates for either TM or BCT. Table 1. Results from multivariable Cox models for factors associated with survival outcomes and IPW adjusted models for factors associated with survival outcomesCox ModelIPW adjusting modelsFactorsHRP95%CIRRP95% CIOSSurgery typeTM without RTBCT0.80.020.70.991.01.00.9-1.1TM with RT1.00.960.81.31.10.60.9-1.3DSSSurgery typeTM without RTRefBCT1.10.40.81.51.20.031.02-1.4TM with RT1.70.0051.22.61.30.021.04-1.6DMFSSurgery typeTM without RTRefBCT1.10.40.91.41.00.50.9-1.2TM with RT1.70.0021.22.40.90.70.7-1.2 LRRSurgery typeTM without RTRefBCT1.30.11.01.71.00.70.7-1.2TM with RT0.40.020.20.90.80.10.6-1.1Subsets IPW adjusted models for factors associated with LRRBCT vs. TM without RTStage I &amp; HR+/HER2-No. of patientsTM without RT/BCTRRP95% CIStage I &amp; HER2+1469/29451.00.90.8-1.3Stage I &amp; TNBC199/2850.70.30.3-1.5Stage II &amp; HR+/HER2-128/3170.4&amp;lt;0.0010.3-0.6Stage II &amp; HER2+690/7451.10.70.7-1.8Stage II &amp; TNBC102/1080.90.50.5-1.4Stage I &amp; HR+/HER2-110/1570.50.0480.3-0.99HER2 – human epidermal growth factor receptor 2; HR – hormone receptor; TNBC – triple negative breast cancer Citation Format: Min Yi, Mariana Chavez Mac Gregor, Benjamin Smith, Abigail S Caudle, Sarah M DeSnyder, Henry M Kuerer, Kelly K Hunt. Comparing survival differences between breast-conserving therapy and mastectomy in patients with early-stage breast cancer undergoing upfront surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-17.

Management of the axilla and the breast after neoadjuvant chemotherapy in patients with breast cancer: A systematic review

Breast cancer is the most common cancer in women worldwide. Breast cancer is traditionally treated with surgery, plus adjuvant systemic therapy and radiotherapy as required. Neoadjuvant chemotherapy (NACT) for the treatment of breast cancer is used for locally advanced operable breast cancer to reduce the tumor size, to perform breast conserving surgery, and to perform a limited axillary approach. Adjuvant chemotherapy for the treatment of inflammatory breast cancer and even in inoperable breast cancer is used to increase overall survival time and to delay disease progression while relieving symptoms. NACT for breast cancer is a new strategy that was introduced toward the end of the 20th century and is increasingly used in the treatment of breast cancer. At present, NACT is increasingly being used to reduce the need for axillary dissection and to convert patients with large tumors to candidates for breast conservation therapy in both locally advanced and operable breast cancers. Breast conserving procedures are currently more preferred by surgeons and axillary dissection is being replaced by sentinel lymph node biopsy after chemotherapy. One of the targets of neoadjuvant systemic therapy is to try to perform a less aggressive surgery by breast conservation, mainly for cosmetic reasons and avoiding axillary dissection mainly for arm mobility, pain, and lymphedema risk. The other target of neoadjuvant systemic therapy is to see the response of the tumor to chemotherapy and determine the treatment accordingly. Neoadjuvant systemic therapy increases the rate of complete pathological response by clearing the breast and axilla from tumor cells before surgery. In this review, we examine the key points of using the NACT in breast cancer, considering radiological imaging methods, surgical management, and reconstruction after NACT.

Abstract PD6-1: BREAST-Q satisfaction and quality of life outcomes in young women undergoing mastectomy and reconstruction for breast cancer

Abstract Background: Young women with breast cancer (BC) often receive aggressive local therapy and are more likely to undergo (bilateral) mastectomy and receive postmastectomy radiation (RT) than older women. Our previous work suggested better quality of life (QOL) outcomes among women undergoing breast conserving therapy (BCT) vs. mastectomy, even with reconstruction (recon), although limited data was available regarding recon. In the current analysis, we sought to understand the impact of recon, accounting for RT, on long-term satisfaction and QOL. Methods: Between 10/2016-11/2017, we administered the BREAST-Q, a validated patient-reported outcomes measure designed to evaluate satisfaction and QOL after breast cancer surgery and recon, to 743 women in the Young Women’s Breast Cancer Study, a multi-site prospective cohort that enrolled women diagnosed (dx’d) at age &amp;lt; 40 from 2006-2016. Demographic and treatment information was obtained by surveys and chart review. Recon was defined as autologous, implant or complex (combination of autologous and implant). Mean BREAST-Q scores for each domain (breast satisfaction, physical, psychosocial, and sexual) were compared by recon types and stratified by receipt of RT; higher BREAST-Q scores (range: 0-100) indicate better QOL. Linear regression was used to identify predictors of BREAST-Q scores. Results: 584 women with Stage 0-3 BC completed the Breast-Q at a median of 5.7 [range 2-10] years from dx), 357 (61%) had mastectomy and recon and were included in the analytic sample. Median age at dx was 36 years; 85% had stage 0, 1 or 2 disease; 41% received RT and 76% underwent bilateral mastectomy. 90.5% underwent immediate recon; of which 65.5% were tissue expander placement. Definitive recon included autologous tissue in 16%; implants in 81% and complex recon in 3%. Mean BREAST-Q breast satisfaction, psychosocial, and physical well-being scores differed based on recon type accounting for RT (Table 1). Significantly lower scores for breast satisfaction were seen in women having implant +RT. Scores were not impacted by bilateral procedure, timing of recon, use of tissue expander, extent of axillary surgery, cancer stage or other treatment factors. In multivariate analyses, receipt of RT, lymphedema and implant-based recon were associated with lower breast satisfaction scores. Physical well-being scores were lower for those with complex recon, for non-White women, for women who reported being financially uncomfortable, for those with lymphedema, and for those &amp;lt;5 years from surgery. Psychosocial well-being scores were lower for women who received RT, had BMI &amp;gt;25, and for those who reported being financially uncomfortable. Sexual well-being scores were lower for women with a BMI &amp;gt;25 and for those who reported being financially uncomfortable. Conclusion Type of recon and receipt of radiation among young survivors who undergo mastectomy and recon for early breast cancer appears to have a differential impact on satisfaction and QOL. Our finding of lower breast satisfaction among young women who received RT, particularly after implant recon, underscores the importance of counseling regarding surgical options, especially for women who may receive RT after mastectomy and who are candidates for BCT. Table 1. Unadjusted BREAST-Q scores stratified by RTBREAST-Q DomainAutologous -RT N=29Autologous +RT N=27Implant -RT N=174Implant +RT N=113Complex N=13Global p-valueSatisfaction with Breasts, mean (sd)67 (19)63 (18)64 (18)53 (18)58 (22)&amp;lt;0.01Physical well-being, mean (sd)81 (13)80 (14)80 (15)77 (14)67 (18)0.01Psychosocial well-being, mean (sd)71 (18)64 (18)72 (20)66 (23)62 (20)0.03Sexual well-being, mean (sd)54 (21)50 (24)52 (20)47 (22)48 (27)0.26RT= radiation Citation Format: Laura Dominici, Jiani Hu, Hee Jeong Kim, Tari King, Kathryn Ruddy, Rulla Tamimi, Jeffrey Peppercorn, Lidia Schapira, Virginia Borges, Stephen Come, Ellen Warner, Julia Wong, Ann Partridge, Shoshana Rosenberg. BREAST-Q satisfaction and quality of life outcomes in young women undergoing mastectomy and reconstruction for breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD6-1.

The Wire and Beyond: Recent Advances in Breast Imaging Preoperative Needle Localization.

Many patients with breast cancer are candidates for breast conservation therapy. This group includes individuals with small nonpalpable tumors detected at screening mammography and those with sufficient tumor shrinkage after neoadjuvant chemotherapy. Breast conservation surgery often requires the use of an imaging-guided preoperative localization procedure, during which a device is placed within or adjacent to the target lesion to guide the surgeon intraoperatively. For decades, wire localization has been the standard for preoperative localization in breast imaging. With this method, a wire is placed in the breast percutaneously, with the distal wire segment positioned adjacent to the abnormality and the proximal wire segment remaining outside the breast. Because of the external component of the wire, the patient must be compliant, and care must be taken to not disturb the wire's position before surgery. Scheduling flexibility is also limited because the wire localization must be performed on the same day as the subsequent surgery. More recently, the available options for performing preoperative localization have expanded greatly and now include the use of nonwire devices such as radioactive and magnetic seeds, radar reflectors, and radiofrequency identification tags. Nonwire localization devices can be placed days in advance of the surgery, at the patient's convenience, to avoid wire-related challenges and complications. They are placed percutaneously within or adjacent to the target breast lesion and detected intraoperatively by using a probe outside the breast.©RSNA, 2019.

The Optimal Approach to Post-Mastectomy and Post-Lumpectomy Breast Reconstruction

The surgical management of breast cancer has changed dramatically over the past 30 years, attributed to improved chemotherapy regimens and a better understanding of tumor biology. There is now a greater emphasis on decreasing surgical morbidity and preserving the breast form. The evolution of oncoplastic surgery has enabled more patients to be candidates for breast-conserving therapy, and the preservation of the entire skin and nipple areolar complex with mastectomy has markedly improved esthetic and patient-reported outcomes. This review provides an overview of the reconstructive options for partial and complete mastectomy, as well as discusses several key factors which markedly influence outcomes.

Do MRI and mammography reliably identify candidates for breast conservation after neoadjuvant chemotherapy?

Neoadjuvant chemotherapy (NAC) may allow breast-conserving therapy (BCT) in patients who require mastectomy at presentation. Breast MRI is more accurate than mammography in assessing treatment response, but combined test reliability in identifying BCT candidates after NAC is not well described. We evaluated whether post-NAC breast MRI alone and with mammography accurately identifies BCT candidates. In this retrospective study of 111 consecutive breast cancer patients receiving NAC, all had pre- and postchemotherapy MRI, followed by surgery. Posttreatment MRI and mammography results were correlated with surgical outcomes and pathologic response. Fifty-one of 111 (46%) patients presented with multicentric or inflammatory breast cancer and were not BCT candidates. The remaining 60 (54%) were considered BCT candidates after downstaging (mean age: 47years). All 60 had at least a partial response to NAC and were suitable for BCT on MRI after NAC. Forty-five of 60 (75%) underwent lumpectomy; 15 of 60 (25%) chose mastectomy. Forty-one of 45 (91%) of lumpectomies were successful; 4 of 45 (9%) required mastectomy. Twelve of 15 (80%) patients choosing mastectomy could have undergone BCT based on pathology; 3 of 15 (20%) did require mastectomy. Two of these three patients had extensive microcalcifications on mammogram, indicating the need for mastectomy despite MRI suitability for BCS. MRI alone correctly predicted BCS in 53 of 60 (88%) patients. MRI plus mammography was correct in 55 of 60 (92%), although only 9 of 45 (20%) BCT patients and 4 of 15 (27%) potentially conservable mastectomy patients had complete pathologic responses. Posttreatment MRI plus mammography is an accurate method to determine whether BCT is possible after NAC is given to downstage disease.

Delay of Adjuvant Chemotherapy After Elective Mastectomy and Immediate Reconstruction in Breast-conservation Candidates

To analyze factors that influence the timing of adjuvant chemotherapy in patients who are candidates for breast-conservation therapy (BCT) but elect mastectomy with immediate reconstruction (M-IR). We identified 35 consecutively treated patients with stage I or II breast cancer between 2004 and 2009 who underwent M-IR and adjuvant chemotherapy from the University of Louisville Cancer Registry. We matched these patients for age and AJCC stage to 35 controls who underwent BCT and adjuvant chemotherapy. We examined the timing and delay of initiation of chemotherapy using univariate logistic regression and McNemar test for matched pairs. For the 70 patients evaluated, the median age was 46 years (range, 30 to 65 y), and the distribution for stage I, IIA, and IIB was 22.9%, 65.7%, and 11.4%, respectively. The 2 groups were well balanced in terms of race, rural/urban status, smoking, diabetes, insurance coverage, and histology. For BCT and M-IR, the median time to chemotherapy initiation was 38 days (range, 25 to 103 d) and 55 days (range, 30 to 165 d), respectively. Patients undergoing M-IR were more likely to experience any delay (>45 d; 54.3% vs. 22.9%; P<0.001) and/or significant delay (>90 d; 20.0% vs. 2.9%; P<0.001). On univariate logistic regression analysis, surgery type had a major impact on delay of chemotherapy (odds ratio=8.35; 95% confidence interval, 2.86-24.4; P<0.001). The use of M-IR in breast-conservation candidates independently predicts for delay in initiation of adjuvant chemotherapy. Further study is needed to qualify the causes and clinical significance of these delays.

Japan Breast Cancer Society clinical practice guideline for surgical treatment of breast cancer.

From 1972 to 1989, 6 randomized controlled trials (RCT) of breast-conserving surgery followed by radiotherapy and radical mastectomy were performed. The two groups did not significantly differ in long-term survival rate after 20 years [1, 2]. Breast-conserving therapy is now a standard of care for Stage I and II breast cancer. As for ductal carcinoma in situ (DCIS), no RCTs compared breast-conserving therapy with mastectomy, but many published case series, reviews and meta-analyses showed good local control rates and high overall survival (OS) results [3]. Most Stage 0–II breast cancers are candidates for breastconserving therapy, but as the EBCTCG’s meta-analysis showed that local recurrence adversely affected survival rates [4], caution is warranted regarding indication or contraindication for breast-conservation therapy and extent of resection.

Surgical considerations for breast cancer patients receiving neoadjuvant systemic therapy

SUMMARY In appropriately selected patients whose tumors respond to neoadjuvant chemotherapy, breast-conserving therapy can be performed with excellent rates of locoregional control. Not all patients become breast-conserving therapy candidates, and in those who require mastectomy, recommendations regarding reconstruction may be influenced by whether a patient will be advised to consider postmastectomy radiation therapy. For patients with clinically node-negative disease, sentinel lymph node dissection performed after neoadjuvant chemotherapy is technically feasible and accurate and results in fewer patients with a positive sentinel lymph node, and therefore fewer patients requiring axillary lymph node dissection. For patients presenting with node-positive disease, a significant percentage will become node-negative with neoadjuvant chemotherapy, and recent trials have been designed to assess the use of sentinel lymph node dissection in select patients.

Impact of neoadjuvant chemotherapy plus HER2-targeting on breast conservation rates: Surgical results from CALGB 40601 (Alliance).

501 Background: Neoadjuvant systemic therapy improves breast conserving therapy (BCT) rates, but the magnitude of this benefit is unknown in operable breast cancer. We sought to quantify this benefit in CALGB 40601, a phase III trial of paclitaxel (T) + HER2 blockade with either trastuzumab (TH), lapatinib (TL), or both (THL), by requiring the treating breast surgeon to determine BCT eligibility before and after neoadjuvant therapy and examining surgical results. Methods: Eligible patients (pts) had operable, newly diagnosed, noninflammatory stage II-III HER2+ breast cancer randomized to receive TH, TL or THL. Prior to, and again after neoadjuvant therapy, the treating breast surgeon determined whether the patient was a BCT candidate based on clinical and radiographic criteria, but the subsequent breast cancer operation was at the discretion of the surgeon and patient. Two endpoints examined were: (1) the conversion rate from BCT-ineligible to BCT-eligible and (2) the rate of successful BCT as determined by tumor-free surgical margins. Results: Of 305 pts randomized (118 THL, 120 TH, 67 TL), 294 were evaluable. Prior to neoadjuvant therapy, 136 (46%) patients were candidates and 158 (54%) were non-candidates for BCT. 107/136 (79%) remained BCT candidates following neoadjuvant therapy and 78 chose BCT, of whom 69 (88%) were successful. 29 pts (21%) initially thought to be BCT candidates became non-candidates after neoadjuvant therapy. Conversely, 76/158 (48%) pts considered non-BCT candidates prior to neoadjuvant therapy down-sized sufficiently to be considered BCT candidates; 40 of these opted for BCT with a 75% (30/40) BCT success rate. In total, 183 pts were deemed BCT candidates after neoadjuvant therapy, yet 65 (36%) proceeded directly to mastectomy. Conclusions: This is the first neoadjuvant trial to prospectively quantify a nearly 50% conversion rate from BCT-ineligible to BCT-eligible in HER2+ breast cancer pts treated with modern systemic therapy. Neoadjuvant chemotherapy combined with targeted anti-HER2 treatment permits potential BCT in approximately 80% of properly selected patients. Clinical trial information: NCT00770809.

Preoperative breast MRI in early-stage breast cancer

Rapid uptake of new imaging technology is a major contributor to rising healthcare costs. Preoperative breast magnetic resonance imaging (MRI) for patients with early-stage breast cancer has dramatically increased in use without the evidence of improved outcomes compared to standard assessment and is associated with higher rates of mastectomy. A decision analytic model was developed to evaluate the impact of adding breast MRI to the preoperative evaluation of women with early-stage breast cancer who were candidates for breast-conserving therapy on patient outcomes measured in quality-adjusted life years (QALYs). Model inputs, including survival, recurrence rates, and health utilities, were obtained from a comprehensive literature review. One-way sensitivity analyses were performed to estimate threshold values for key parameters at which adding MRI would become the optimal imaging strategy over standard assessment. Preoperative MRI resulted in 17.77 QALYs compared to 17.86 QALYs with standard assessment, a decrease of 0.09 QALYs or 34 days. In sensitivity analyses, standard assessment was associated with better patient outcomes than preoperative breast MRI across all plausible probabilities for mastectomy, local recurrence, and health utilities. For routine preoperative breast MRI to become the optimal strategy, the conversion rate to mastectomy after preoperative MRI would need to be <1 % (versus the range of 3.6-33 % reported in the literature). Routine preoperative breast MRI appears to confer no advantage over the standard diagnostic evaluations for early-stage breast cancer and may lead to worse patient outcomes.

The role of preoperative bilateral breast magnetic resonance imaging in patient selection for partial breast irradiation in ductal carcinoma in situ.

Purpose. Women with ductal carcinoma in situ (DCIS) are often candidates for breast-conserving therapy, and one option for radiation treatment is partial breast irradiation (PBI). This study evaluates the use of preoperative breast magnetic resonance imaging (MRI) for PBI selection in DCIS patients. Methods. Between 2002 and 2009, 136 women with newly diagnosed DCIS underwent a preoperative bilateral breast MRI at Mayo Clinic in Florida. One hundred seventeen women were deemed eligible for PBI by the NSABP B-39 (National Surgical Adjuvant Breast and Bowel Project, Protocol B-39) inclusion criteria using physical examination, mammogram, and/or ultrasound. MRIs were reviewed for their impact on patient eligibility, and findings were pathologically confirmed. Results. Of the 117 patients, 23 (20%) were found ineligible because of pathologically proven MRI findings. MRI detected additional ipsilateral breast cancer in 21 (18%) patients. Of these women, 15 (13%) had more extensive disease than originally noted before MRI, and 6 (5%) had multicentric disease in the ipsilateral breast. In addition, contralateral breast cancer was detected in 4 (4%). Conclusions. Preoperative breast MRI altered the PBI recommendations for 20% of women. Bilateral breast MRI should be an integral part of the preoperative evaluation of all patients with DCIS being considered for PBI.

P2-16-05: Delay of Adjuvant Chemotherapy after Elective Mastectomy and Immediate Reconstruction in Breast Conservation Candidates: A Matched-Pair Analysis.

Abstract Background: To analyze factors that influence the timing of adjuvant chemotherapy in patients who are candidates for breast conservation therapy (BCT) but elect mastectomy with immediate reconstruction (M-IR). Methods: Using data from the University of Louisville Cancer Registry, we identified 35 consecutively-treated patients with stage I or II breast cancer between 2004 and 2009 who underwent M-IR and adjuvant chemotherapy. These were matched for age and AJCC stage to 35 controls who underwent BCT and adjuvant chemotherapy. We examined the timing of initiation of chemotherapy from the date of surgery and assessed the probability of therapeutic delay using univariate logistic regression and McNemar's test for matched pairs. Results: For the 70 patients included in this study, the median age was 46y (range: 30–65y), and the distribution for stage I, IIA and IIB was 22.9%, 65.7% and 11.4%, respectively. The two groups were well balanced in terms of race, rural/urban status, smoking, diabetes, insurance coverage, and histology. The median time to initiation of adjuvant chemotherapy was 38 days (range: 25–103 days) for BCT and 55 days (range: 30–165 days) for M-IR. Patients undergoing M-IR were more likely to experience any delay (&amp;gt; 45 days; 74.3% vs. 25.7%, p &amp;lt; 0.001) and/or significant delay (&amp;gt;90 days; 20.0% vs. 2.9%, p &amp;lt; 0.001) than those choosing BCT. On univariate logistic regression analysis, the extent of surgery had a major impact on the likelihood of any delay in chemotherapy (OR= 8.35, 95% C.I. = 2.86−24.3, p &amp;lt;0.001). None of the other aforementioned factors predicted for delay. Conclusion: The use of elective mastectomy with immediate reconstruction in breast conservation candidates independently predicts for delay in initiation of adjuvant chemotherapy. Further study is needed to qualify the underlying causes of and ultimate clinical significance of these delays. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-05.

Preoperative breast MRI in early-stage breast cancer: A decision analysis.

6035 Background: Rapid uptake of new imaging technology is a major contributor to rising health care costs. Preoperative breast magnetic resonance imaging (MRI) for patients with early-stage breast cancer has dramatically increased in use without evidence of improved outcomes compared to standard triple assessment (clinical examination, imaging with mammography and/or ultrasonography, and needle biopsy) and is associated with higher rates of mastectomy. Methods: A decision analytic model was developed to evaluate the impact of adding breast MRI to the preoperative evaluation of women with early-stage breast cancer who were candidates for breast-conserving therapy (BCT) on patient outcome measures in quality-adjusted-life-years (QALYs). Model inputs including survival, recurrence rates, and health utilities were obtained from a comprehensive literature review. One-way sensitivity analyses were performed to estimate threshold values for key parameters at which adding MRI would become the optimal imaging strategy over standard triple assessment. Results: Preoperative breast MRI was associated with a decrease of 0.094 QALYs compared with no MRI, based on a 20-year life expectancy after diagnosis of early-stage breast cancer. In order for routine preoperative breast MRI to become the optimal strategy, the conversion rate to mastectomy after preoperative MRI would need to be <1% (vs. range of 3.6-54% reported in the literature) Across a wide range of local recurrence rates following BCT, MRI remained inferior to no MRI. Conclusions: Routine preoperative breast MRI appears to confer no advantage over standard diagnostic evaluations for early-stage breast cancer and may lead to worse outcomes.

Impact of Progression during Neoadjuvant Chemotherapy on Operative Management of Breast Cancer.

Abstract Background: Neoadjuvant chemotherapy (NCT) is the standard of care for locally advanced breast cancer, but remains controversial in early stage disease. Some have raised concerns that disease progression may make breast-conserving therapy (BCT) or even mastectomy impossible. The goal of this study was to determine the impact of disease progression during NCT on operative management. Methods: We reviewed clinicopathologic data on patients receiving NCT for Stage I-III breast cancer at a cancer center between 1994 and 2007. Chemotherapy regimens were anthracycline and/or taxane-based as determined by the medical oncologist. Results: 1928 patients received NCT, of which 1762 (91%) had a response (minor, partial, or complete), 107 (6%) had stable disease (SD), and 59 (3%) progressed (PD) on at least one regimen. Of the 59 patients with progression, 13 (22%) had tumor response and 7 (12%) had SD with their first regimen, but progressed on their second regimen. Thirty-nine (66%) had progression on their first regimen of which 4 (10%) proceeded to surgery, 1 (3%) developed metastasis, and 1 (3%) refused further therapy. Thirty-three (85%) received a second chemotherapy regimen after progression on the first regimen; 18 (55%) had response to the second regimen, 5 (15%) had SD, and 10 (30%) had further progression. Eight (14%) had XRT to control local progression. In the 59 patients with progression at any point during NCT, 40 (68%) underwent mastectomy, 12 BCT (20%), and 7 (12%) had no surgery. In patients who had mastectomies, 3 (8%) were BCT candidates before progression, one (3%) was converted to mastectomy for technical reasons, and 2 (5%) were not evaluable from available data. Overall, disease progression changed the operative plan in 11 (0.5%): 2 developed distant metastasis, 2 developed clinical lymphadenopathy, 3 required mastectomy instead of BCT, 3 became inoperable, and 1 required flap closure. Conclusion: Patients treated with NCT should be evaluated by multi-disciplinary team members for response to therapy. Progression on NCT is infrequent (3%), but the optimal management in these patients needs further study. Overall, progression on NCT changes the operative management in only a small proportion of patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1090.

Determinants of Breast Conservation Rates: Reasons for Mastectomy at a Comprehensive Cancer Center

Bias in referral patterns and variations in multi-disciplinary management may impact breast conservation therapy (BCT) rates between hospitals. Retrospective studies of BCT rates are limited by their inability to differentiate indicated mastectomies versus those chosen by the patient. Our prospective breast cancer data base was queried for patients with invasive breast cancer who underwent surgical therapy at the University of Michigan over a 3-year period. Demographics, stage and histology were recorded along with the reason mastectomy was performed, categorized as "by need" (contraindication to BCT) or "by choice." Multivariate analysis was used to identify factors significantly associated with mastectomy by choice. BCT was associated with tumor size, histology and nodal status, but not older age, either by choice or by need. Of the 34% of patients initially felt to be poor candidates for BCT, it was absolutely contraindicated in 44%, while 56% were thought to have a tumor-to-breast size ratio too large for successful BCT. Of this latter group, 80% underwent neo-adjuvant chemotherapy in an attempt to downstage the primary tumor and perform BCT, which was successful in over half the patients. For the patients initially thought to be good candidates for BCT, only 15% chose to undergo mastectomy, while 5% eventually required mastectomy due to failed attempts to achieve negative margins. Overall, the BCT rate was 63%, however without the use of neo-adjuvant chemotherapy, the BCT rate would have been only 53%. At a tertiary referral center, BCT rates are driven more by contraindications than patient choice, and may be heavily skewed towards mastectomy due to referral patterns. In addition to tumor factors such as stage and histology, BCT rate can be dramatically impacted by neo-adjuvant chemotherapy or genetic counseling. Examining BCT rates alone as a measure of quality, therefore, is not an appropriate standard across institutions serving diverse populations.

Comparison of FDG PET and MRI for evaluating the tumor extent of breast cancer and the impact of FDG PET on the systemic staging and prognosis of patients who are candidates for breast-conserving therapy

FDG PET has not yet found a role in the clinical evaluation of the tumor extent of breast cancer. FDG PET has been reported to be useful for evaluating the prognoses of breast cancer patients with more accuracy than conventional imaging modalities. The purpose of this study was to compare the accuracy of FDG PET and MRI for the preoperative assessment of the tumor extent of breast cancer, for evaluating the impact of FDG PET on systemic staging, and also for predicting the prognosis of patients who are candidates for breast-conserving therapy. The study was a prospective series of 23 breasts with breast cancer that underwent both FDG PET and MRI before surgery. Systemic staging with FDG PET was also performed. The correlation between the results of these examinations and histological findings was thus examined. The maximum standardized uptake value (SUVmax) of the tumors was investigated in association with the patient prognoses. When evaluating the local tumor extent, the accuracy of FDG PET (43.5%) was significantly lower than that of MRI (91%) (P < 0.001). The sensitivity, specificity, and accuracy of FDG PET regarding the nodal status were 60, 94, and 87%, respectively. No patients demonstrated any distant metastasis, whereas FDG PET gave a false positive in one patient. The mean follow-up period was 61 months. The SUVmax value of the worse prognosis patient group was significantly higher than that of the good prognosis patient group (P = 0.032). FDG PET is not a breast imaging modality for evaluating the local tumor extent, but it is useful for predicting the prognoses of patients who are candidates for breast-conserving therapy.