Candidates For Breast Conservation Research Articles

Abstract P2-12-16: The use of oncoplastic surgical techniques to increase successful breast conservation in invasive lobular carcinoma of the breast

Abstract Background: Invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma in its non-cohesive growth pattern. These diffuse tumors pose challenges for accurate size assessment as well as surgical resection. Patients with ILC have higher rates of positive margins and lower rates of successful breast conservation surgery. Oncoplastic surgical techniques such as oncoplastic reduction mammoplasty and lumpectomy with oncoplastic closure can allow for removal of larger areas of breast tissue than lumpectomy alone. Whether or not these techniques improve the success of breast conservation in patients with ILC is unknown. Methods: We queried a prospectively maintained surgical database and identified 384 women treated for ILC at UCSF between 1992 and April 2017. We reviewed pathology and operative reports, and clinical outcomes data, and identified 199 women who had an initial attempt at breast conservation. Data were analyzed in Stata 14.2. Results: Average age was 61 years (range 39-84), and 69% of patients underwent lumpectomy, 16% had lumpectomy with oncoplastic closure, and 15% had oncoplastic reduction mammoplasty. The majority of tumors were hormone receptor positive, Her2 negative, grade 2, T1 or T2, and 28% were node positive. A total of 156 women (78%) had successful breast conservation; of these, 34% had one re-excision, and 1 patient had two re-excisions. Positive margins were seen in 40% of patients overall, and were significantly lower in the lumpectomy with oncoplastic closure group and those who had shave margins taken. Among the patients who underwent lumpectomy only, obtaining shave margins was significantly associated with final negative margins (71% versus 53%, p = 0.033). Patients with oncoplastic reduction mammoplasty had significantly larger average tumor size (4.1 cm), and significantly more tissue removed (167 cm3). LumpectomyLumpectomy with oncoplastic closureOncoplastic reduction mammoplastyP valueTumor size (mean)2.4 cm2.1 cm4.1 cm<0.001Volume tissue excised65 cm383 cm3167 cm3<0.001Positive margins42%19%50%0.022Shave margins50%69%79%0.005Successful breast conservation75%97%77%0.021Re-excision rate among those with successful breast conservation33%26%39%0.571 Conclusions: Tailoring the surgical treatment to tumor size can increase the rate of successful breast conservation surgery for these diffuse, often non-palpable lobular cancers. For the women with the largest tumors, oncoplastic reduction mammoplasty was often recommended. This group likely represents women who were borderline candidates for breast conservation; despite this, oncoplastic reduction mammoplasty allowed 77% to ultimately have successful breast conservation. For the women with smaller tumors, removing additional tissue with shave margins and using oncoplastic techniques for closure when necessary clearly reduced positive margin rates. Surgeons should routinely obtain shave margins when performing partial mastectomy for women with ILC. Citation Format: Wong JM, Piper ML, Ewing C, Alvarado M, Esserman LJ, Sbitany H, Foster RD, Mukhtar RA. The use of oncoplastic surgical techniques to increase successful breast conservation in invasive lobular carcinoma of the breast [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-12-16.

Rationale for Mastectomy after Neoadjuvant Chemotherapy

Neoadjuvant chemotherapy (NAC) reduces tumor size, facilitating the use of breast conservation surgery (BCS). However, mastectomy remains the surgical outcome for certain women. The goal of this study was to determine the rationale for mastectomy after NAC, particularly in women eligible for BCS. Retrospective data were reviewed on patients who received NAC between February 2006 and August 2010 at our institution. Demographics and tumor characteristics were compared between patients who received BCS and mastectomy after NAC. Of 149 patients meeting inclusion criteria, 102 (68%) underwent BCS and 47 (32%) underwent mastectomy. Patient preference was the most common rationale for mastectomy (n = 19; 40%), followed by extent of disease (n = 13; 28%), presence of a breast cancer susceptibility gene (BRCA) mutation (n = 9; 19%), persistent positive margins (n = 5; 11%), and wound complications (n = 1; 2%). Of the 47 patients who underwent mastectomy, 37 (79%) were eligible for BCS after NAC. Larger pathologic tumor size (2.05 vs 1.25 cm, P = 0.04) and lobular histology [invasive lobular carcinomas, n = 12/17 (70%) vs invasive ductal carcinomas, n = 36/133 (27%); P < 0.01] were associated with increased rate of mastectomy. After NAC, patient preference, extent of disease, and the presence of a BRCA mutation account for the vast majority of mastectomies. Interestingly, most of these patients were shown to be candidates for breast conservation. This highlights the importance of educating patients about their surgical choice and the lack of evidence, showing a benefit to more extensive surgery.

Batwing versus Wise pattern mammoplasty for upper pole breast tumours: a detailed comparison of cosmetic outcome

BackgroundThe aim of this study is to compare the results of batwing mammoplasty and Wise pattern mammoplasty in the surgical management of upper pole breast tumours.MethodsThis is a retrospective observational study including 126 breast cancer patients who presented between 2009 and 2015 to the National Cancer Institute of Cairo University in Egypt. All patients were candidates for breast conservation, with upper pole tumours, which was defined as tumours between 3 and 9 o’clock. Patients were categorized into two groups. Group A (64) included patients who underwent inferiorly based therapeutic mammoplasty, while group B (62) was designated for patients who had batwing mammoplasty. The results of both groups were compared and analyzed.ResultsWise pattern mammoplasty group had statistically significant higher complication rate. The overall aesthetic result of Wise pattern technique was superior to batwing mammoplasty. However, batwing mammoplasty showed a statistically significant higher rate of patient satisfaction.ConclusionsBoth techniques are valid options for upper pole breast tumours. Wise pattern therapeutic mammoplasty remains aesthetically superior; however, batwing mammoplasty is an easy, simple technique with acceptable results to patients.

Abstract P6-12-06: Preoperative chemotherapy regimens and breast cancer subtype in an underinsured Hispanic population

Abstract Background: Although the Hispanic population is among the fastest growing in the United States, however, less is known about them then other populations. Breast cancer in different racial/ethnic populations display different behaviors. The current study was performed to examine response to preoperative chemotherapy regimen and by breast cancer subtype in a Hispanic safety net population. Methods: A retrospective review of Hispanic breast cancer patients who underwent preoperative chemotherapy from July 2001 to February May 2015 at a safety net hospital. Sociodemographic, clinical, and treatment variables were evaluated. Response to chemotherapy regimen was recorded. Breast cancer subtypes were divided based on IHC and FISH testing. Luminal B subtype was classified based on Ki67 (&amp;gt;15%) and PR (&amp;lt;20%). Results: The average age of the 133 patients was 45 years. 93% of the patients were insured with Medicaid or uninsured (70%). The average size of the cancers at presentation was 5cm. Overall 86% of patients had a clinical response to preoperative chemotherapy and 35% had pathologic complete response (pCR). AC and TC regimens had the lowest rate of pCR at 16%. AC/T (every 3 week and weekly) had similar rates of pCR 23% and 29%, while dose dense regimens showed pCR 40%. Herceptin containing regimens had pCR 57%. 7 patients received TAC and 71% had pCR. By subtype, Luminal A and B patients had low rates of pCR 9% and 14% respectively. Luminal B patients did benefit from preoperative chemotherapy as 86% of patients who were not candidates for breast conservation at presentation were able to undergo lumpectomy after preoperative chemotherapy. Her2 subtype patients who got Herceptin had pCR 57%. Triple negative patients had pCR 54%. Conclusions: In this underinsured, Hispanic population who presented at advanced stages, differences in response to preoperative chemotherapy were seen based on breast cancer subtype. Differences were also seen based on chemotherapy regimen. TAC maybe a particularly effective regimen in triple negative Hispanic women. Citation Format: Mehta D, Winton L, Walters J, Hsu C-H, Nodora J, Martinez ME, Bouton M, Komenaka IK. Preoperative chemotherapy regimens and breast cancer subtype in an underinsured Hispanic population. [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 P6-12-06.

Breast-conserving surgery in patients with Paget's disease.

Paget's disease of the breast is a rare condition that is associated with underlying breast cancer in the majority of patients. The conventional treatment for Paget's disease has been mastectomy, but there is an increasing trend to consider breast-conserving surgery (BCS) in selected patients. Owing to the uncommon nature of the disease, research studies tend to be small and retrospective. This systematic review presents the published evidence regarding BCS for patients with Paget's disease with a focus on patient selection and oncological safety. A search of Ovid and PubMed databases was conducted to identify all papers published regarding BCS for Paget's disease. The search identified 172 papers of which 43 were clinically relevant. BCS is a safe alternative to mastectomy, provided a clear surgical margin is achieved and adjuvant radiotherapy used. However, patients with Paget's disease should be assumed to have underlying breast cancer, and these cancers tend to have poor biological profiles. When BCS is considered, careful preoperative investigation should be undertaken to identify the presence and extent of an underlying cancer. These cancers can be mammographically occult, multifocal or multicentric. Although the evidence is limited, there may be a role for MRI in selecting patients with Paget's disease for BCS. Patients with Paget's disease are candidates for breast conservation with appropriate preoperative investigations. Oncological outcomes are equivalent to those of mastectomy if surgical margins are achieved and adjuvant radiotherapy is given.

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.

Impact of neoadjuvant chemotherapy on locoregional surgical treatment of breast cancer.

Preoperative (neoadjuvant) chemotherapy (NC) has become the standard of care for patients with locally advanced breast cancer and is being increasingly used in those with large operable disease. Its main clinical advantages from a surgical therapy standpoint include the potential for conversion of patients requiring mastectomy to breast-conservation candidates, the potential for improving the cosmetic outcome following lumpectomy by decreasing the size of the primary breast tumor even if the patient is a lumpectomy candidate at presentation, and the potential for converting patients who present with positive axillary nodes and who would initially require axillary lymph node dissection to candidates for sentinel lymph node biopsy alone. Important steps are required from the time of diagnosis until the time of surgical resection to ensure successful locoregional therapy outcomes in patients treated with NC. They include accurate assessment of the location and extent of the primary breast tumor and determination of axillary nodal status before and after NC. This information is critical for successful execution of the surgical plan and to optimize the use of adjuvant radiotherapy following NC. In the future, development of more active neoadjuvant chemotherapy regimens and novel molecular and imaging techniques will undoubtedly lead to further individualization of breast cancer surgical management following NC, including the possibility of avoiding surgical resection in cases with a high likelihood of achieving a pathological complete response.

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.

Defining a Role and Predicting Benefit From Platinum-Based Therapy in Breast Cancer: An Evolving Story

There are three evolving stories that have the potential to improve outcomes for patients with localized triple-negative breast cancer (TNBC), a phenotypically defined breast cancer subtype that often occurs in individuals harboring germline BRCA1 mutations, including up to 20% of unselected individuals and 50% with a strong family history. When occurring sporadically without a germline mutation, TNBC shares many clinical and molecular features with BRCA1associated cancers, including defective DNA repair, which may be a result of methylation-induced silencing of BRCA or mutations in other genes that encode proteins involved in DNA repair. The first story, as exemplified in the article by Sikov et al that accompanies this editorial, is that the DNA–damaging agent carboplatin significantly improves the pathologic complete response (pCR) rate when added to a neoadjuvant chemotherapy regimen that includes a taxane, anthracycline, and alkylating agent, confirming the results of a similar trial. The second story involves using predictive biomarkers to identify tumors that are particularly sensitive to DNA-damaging agents, including germline mutations in genes that encode proteins that are essential for DNA damage repair and somatic markers that identify so-called BRCAness in sporadic cancers. The third story centers on using response to neoadjuvant therapy as a pharmacodynamic biomarker, exemplified by the strong inverse association between pCR in the breast and axilla and risk of recurrence. Although it is clear that platinum-containing agents are potentially useful in TNBC, it is unclear which patients benefit from them and how to best use them. The platinum story in breast cancer dates back to 1988, when Sledge et al noted partial responses in seven of 19 patients (47%) unselected for breast cancer subtype who received cisplatin as first-line therapy for metastatic disease. Other reports followed, confirming activity for cisplatin and carboplatin when used as first-line cytotoxic therapy in otherwise unselected patients, although efficacy was limited when used beyond first-line treatment, and attempts to combine platinum-containing agents with taxanes met with variable success. On the basis of preclinical data indicating synergy when platinum-based drugs were combined with trastuzumab in human epidermal growth factor receptor 2 (HER2)/neu positive disease, the carboplatin-docetaxel-trastuzumab regimen was found to be an effective adjuvant regimen, although adding carboplatin to a trastuzumab-taxane regimen in metastatic disease produced only modest clinical benefit. This brings us to the next chapter in the evolving platinum story, which includes two randomized phase II neoadjuvant trials in TNBC. The first report of the GeparSixto trial by von Minckwitz et al included 293 patients with operable and locally advanced TNBC who received weekly paclitaxel and liposomal doxorubicin plus bevacizumab, either alone or in combination with weekly carboplatin (area under the curve [AUC] 2, then reduced to AUC 1.5) for up to 18 weeks. The addition of carboplatin significantly improved the pCR rate in the breast and axilla (58% v 37%; P .05), although it also substantially increased toxicity without affecting breast conservation rates. The second study, by Sikov et al from the Alliance Clinical Trials Group, included 493 patients with operable and locally advanced TNBC who received weekly paclitaxel for 12 weeks followed by doxorubicin-cyclophosphamide every 2 weeks. Paclitaxel was given alone or in combination with carboplatin (AUC 6 every 3 weeks for four cycles); using a 2 2 factorial design, patients were also randomly assigned to receive chemotherapy alone or in combination with bevacizumab. The addition of carboplatin was associated with an improved pCR rate in the breast and axilla (54% v 41%; P .0029); similar benefits were observed in the absence (49% v 39%) and presence (60% v 43%) of bevacizumab. Although numerically more patients who were not initially considered candidates for breast conservation were deemed potential candidates after therapy when carboplatin was used (57% v 44%), the difference was not statistically significant, and the actual rates were not reported. Neither trial was adequately powered to determine carboplatin-reduced recurrence, nor were patients observed long enough to observe such a difference if it existed. Why use platinum-containing agents in TNBC? This brings us to our second evolving story, dating back to 2000, when it was recognized that BRCA-mutant cells were sensitized to the antineoplastic effects of DNA-damaging agents such as platinum, and that neoadjuvant platinum monotherapy was highly effective in BRCA mutation– associated breast cancer. It was also recognized that sporadic TNBC JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 1 JANUARY 1 2015

Abstract P5-15-09: A new method for marking the lumpectomy cavity during oncoplastic surgery and breast conservation

Abstract Background: Oncoplastic surgery has dramatically improved patient outcomes following breast conservation, however, most patients require adjuvant radiation therapy following surgery. Adjuvant radiation is essential in order to decrease local recurrence rates, yet marking and identifying the exact location of the tumor bed that requires radiation remains challenging. This is particularly true when oncoplastic surgery is used to bring local tissue flaps into the area in order to reconstruct the defect created by surgical excision. Many surgeons currently place clips at various positions within the cavity in order to help define the target area. Alternatively, if no clips are placed, postoperative tissue changes visible on CT scan are used to determine the target location. Unfortunately, both of these current methods are imprecise and can be misleading for radiation treatment planning resulting in over or under estimation of the planned treatment volume. Given the shortcomings of current methods for targeting the lumpectomy cavity, we evaluated the utility of a new 3-dimensional bioabsorbable tissue marker as a more standardized approach. Methods and Materials: 40 patients with Stage I or II breast cancer were implanted with the BioZorb™ tissue marker (Portola Valley, CA) during partial mastectomy. All patients had pre-operative staging to insure they were appropriate candidates for breast conservation. Following excision of the tumor, a BioZorb tissue marker was sutured into the cavity. In some cases, oncoplastic techniques (including mobilization of glandular flaps) were used to reconstruct the defect from the partial mastectomy. The flaps were sutured through and around the BioZorb. In other cases, the walls of the lumpectomy cavity and the overlying tissue flaps were sutured to the BioZorb as a structural element. In all cases, the margins of the excision site were approximated to the edges or through the center of the tissue marker. Results: The surgical marker was easily inserted in all cases, and was clearly visualized with clinical imaging in all patients. Insertion did not interfere with surgical techniques, nor did it preclude concomitant surgical procedures such as wire localization, sentinel lymph node biopsy and/or breast reconstruction with oncoplastic techniques. Radiation treatment planning was easier and more precise based upon the visibility of the bioabsorbable and permanent components of the marker. The marker decreased boost volume significantly, and was particularly useful for radiation planning when there was no remaining seroma cavity at the surgical site. Conclusions: This novel 3-D bioabsorbable tissue marker reliably marked the area of surgical excision in a standardized fashion. Both the bioabsorbable and permanent clips within the marker are useful for radiation treatment planning and clinical follow-up of the surgical site. The marker was particularly useful in defining the surgical area when oncoplastic techniques were used to close the surgical cavity, and/or when no remaining seroma was present. This new method of marking the cavity allows for marked improvement in radiation treatment planning and may facilitate the use of advanced techniques in radiation delivery as well. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-15-09.

Increasing Use of Elective Mastectomy and Contralateral Prophylactic Surgery Among Breast Conservation Candidates

First-line surgical options for early-stage breast cancer include breast-conserving surgery (BCS) or mastectomy. We analyzed factors that influence the receipt of mastectomy and resultant trends over time. We analyzed the rates of mastectomy and BCS for 1634 women who underwent upfront surgical treatment for AJCC stage 0, I, or II breast cancer between 1995 and 2008 using data from the University of Louisville James Graham Brown Cancer Center Tumor Registry. We examined the trend of treatment over time and assessed the probability of receiving mastectomy using multivariate logistic regression. Overall, 65.9% of women received BCS, and 34.1% received mastectomy over a 14-year period (annual BCS rate range, 38.6% to 77.7%). The mastectomy rate substantially decreased from 43.5% in 1995 to 22.5% in 2004 (P = 0.0007) but then increased to 51.7% in 2008 (P < 0.0001). During the years between 2004 and 2008 (vs. 1995 to 2003), there was a significant increase in the rates of mastectomy performed in conjunction with immediate reconstruction (IR: 35.7% vs. 8.4%; P < 0.0001) and/or contralateral prophylactic mastectomy (CPM: 22.9% vs. 3.3%; P < 0.0001). On the basis of the multivariate analysis, the rate of receiving mastectomy was drastically higher for patients treated since 2004 (vs. before 2004), uninsured and government-insured (vs. privately insured) patients, patients with pT2 disease (vs. pTis or pT1), patients with pN1 disease (vs. pNX or pN0). In this longitudinal registry study, major independent determinants of mastectomy for early-stage breast cancer include year of diagnosis, insurance status, and stage. Mastectomy rates declined until 2004, but have since increased in conjunction with immediate reconstruction and contralateral prophylactic mastectomy. Additional study is needed to identify the underlying reasons for and unintended consequences of the reemergence of radical surgery for early-stage breast cancer in the era of multidisciplinary care.

Breast-Specific Gamma Imaging Influences Surgical Management in Patients with Breast Cancer

Breast-specific gamma imaging (BSGI) is a physiologic breast imaging modality that provides more sensitive detection of breast lesions than mammography or ultrasound, and appears to have greater specificity than breast MRI. The purpose of this study was to evaluate how often BSGI changed surgical management in patients with breast cancer. Charts were reviewed from 218 consecutive eligible patients who had preoperative evaluation with BSGI or MRI before surgery for breast cancer from January 2008 to May 2010. Patients who were initially considered eligible for breast-conserving therapy (BCT) were evaluated to determine how many ultimately had mastectomies. Patients who underwent mastectomy because of personal choice or ineligibility for BCT were excluded. Management was changed to mastectomy in 11.9% of those who had BSGI and 28.9% of those who had MRI. Review of pathology demonstrated that all patients who underwent mastectomies were not candidates for breast conservation. 15.4% of patients who underwent BCT based on BSGI findings required a single re-excision due to positive surgical margins. 14.4% required mastectomy. In the MRI group, 18.8% required a single re-excision, and 6.3% required mastectomy. Evaluation with BSGI changed management to mastectomy in a substantial proportion of patients believed to be eligible for BCT following standard imaging. BSGI is effective in evaluation of extent of disease in patients with breast cancer, and is comparable to MRI in terms of its influence on surgical management.

The role of breast magnetic resonance imaging on surgical treatment planning of breast cancer

To determine the frequency by which breast magnetic resonance imaging (MRI) provides information that influences the surgical management of patients with breast cancer. From August 2006 to December 2008, contrast-enhanced bilateral breast MRI was performed on 68 patients, all of whom exhibited highly suspicious imaging findings (BI-RADS category 4 or 5). Patients were grouped according to their histopathological diagnosis and type of breast parenchyma. All of the enrolled patients were believed to be candidates for breast conservation on the basis of physical examination, mammography, and ultrasonography. The patients were reevaluated with the MRI examination as to whether they were still candidates for breast conservation therapy. The MRI findings changed the previous management plans in 19.1% of the 68 patients. With respect to the surgical approach, no statistically significant difference was observed between the histopathology groups (P = 0.403). In terms of the breast parenchymal pattern, however, surgical planning was changed in 53.8% of the patients who exhibited a dense pattern, which was significantly different from the rates of the other groups (P = 0.006). The sensitivity, specificity, positive predictive value, and negative predictive value of the MRI for additional malignant lesion detection and identification were 85%, 98%, 92%, and 96%, respectively. The agreement test revealed 86% agreement (very good) between the additional findings observed on the MRI and the histopathological results. If breast-conserving surgery is planned, an MRI should be performed in all women with suspected breast cancer, especially those exhibiting dense or heterogeneously dense breast parenchyma, for which the sensitivity of both ultrasonography and mammography is low.

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.

The Role of Lapatinib in the Preoperative Therapy of Breast Cancer

Preoperative or neoadjuvant chemotherapy is a well-established modality in the treatment of nonmetastatic breast cancer. Patients initially considered inoperable may be able to achieve operable status after preoperative chemotherapy and patients initially considered not to be candidates for breast conservation may convert to breast conservation status. Human epidermal growth factor receptor 2 (Her2)-positive tumors have been shown to have a more aggressive course including early local relapse and metastasis when compared to Her2-negative breast cancers, but the optimal use of Her2-targeted agents is constantly evolving as new agents become available. Preoperative studies allow us to quickly assess the activity of new agents and combinations for particular biological subsets of breast cancer.

Role of primary site local management for advanced breast cancer patients

Patients with locally advanced disease are a heterogeneous group including those with T3N1, T0-3N2-3 and T4N0-disease. Multimodality therapy is requested for locally advanced breast cancer with focus on neoadjuvant chemo/hormonal therapy to downstage the cancer and improve operability (1). Attention has been focused in identifying patients with excellent response to pre-operative therapy who are possible candidates for breast conservation (2). In these patients the goal is the optimal loco-regional control with acceptable cosmesis.

Increasing use of mastectomy with immediate reconstruction and contralateral prophylactic mastectomy in breast-conservation candidates: A 14-year report from a comprehensive cancer center.

1104 Background: First-line surgical options for early stage breast cancer include breast-conserving surgery (BCS) or mastectomy. We analyzed factors that influence the receipt of mastectomy and resultant trends over time. Methods: We analyzed the rates of mastectomy and BCS for 1,634 women who underwent up-front surgical treatment for AJCC stage 0, I or II breast cancer between 1995 and 2008 using data from the University of Louisville James Graham Brown Cancer Center Cancer Registry. We examined the trend of treatment over time and assessed the probability of receiving mastectomy using multivariate logistic regression. Results: Overall, 65.9% of women received BCS and 34.1% received mastectomy over a 14-year period (annual BCS rate range: 38.6-77.7%). The mastectomy rate substantially decreased from 43.5% in 1995 to 22.5% in 2004 (p=0.0007), but then increased to 51.7% in 2008 (p<0.0001). During the years between 2004-2008 (vs. 1995-2003), there was a significant increase in the rates of mastectomy performed in conjunction with immediate reconstruction (IR: 35.7% vs. 8.4%; p<0.0001) and/or contralateral prophylactic mastectomy (CPM: 22.9% vs. 3.3%; p<0.0001). Based on the multivariate analysis, the rate of receiving mastectomy was drastically higher for patients treated since 2004 (vs. prior to 2004), uninsured and government-insured (vs. privately insured) patients, patients with pT2 disease (vs. pTis or pT1), patients with pN1 disease (vs. pNX or pN0). Conclusions: In this longitudinal registry study, major independent determinants of mastectomy for early stage breast cancer include year of diagnosis, insurance status, and stage. Mastectomy rates declined until 2004, but have since increased in conjunction with IR and CPM. Additional study is needed to identify the reasons for and consequences of the reemergence of radical surgery for early stage breast cancer in the era of multidisciplinary care.

Breast conservation (BCT) for DCIS: A prospective study of how MRI impacts management (MGMT).

546 Background: The optimal role of MRI in the MGMT of patients (pts) with DCIS remains undefined. We undertook this prospective study to evaluate the changes in MGMT that occur due to MRI findings. Methods: 100 pts <60 y.o. with core biopsy-proven DCIS (± microinvasion) were prospectively enrolled. After evaluation with mammography ± ultrasound (US), the operative plan was recorded. 86 were BCT candidates. Additional (addl) suspicious MRI findings and subsequent MGMT changes were then prospectively recorded. Significance was tested by chi squared. Results: See Table. Of 41 pts with addl MRI findings, 12 had BCT with 1 excision, 16 had attempted BCT but required subsequent TM or reexcision, 5 had TM as 1st operation a result of MRI, 17/41 (41%) had 1 operation. Of 45 pts with no additional MRI findings, 28 had BCT with 1 excision, 17 had attempted BCT but required TM or reexcision. 28 (62%) had 1 operation. Overall, MRI altered MGMT in 32/86 (37%) pts. Of these, 9 (10%) were spared an operation. To benefit these 9 pts, 28 procedures in 19 (22%) pts were generated. Among pts with no addl MRI findings, BCT was more likely to be successful (84% vs. 56%, p= 0.004) and to require 1 operation (62% vs. 29%, p= 0.002). Among pts with addl MRI findings, TM was more likely to be elected by pts (20% vs. 0%, p=0.002) or required (24% vs. 16%, p=0.3). Conclusions: MRI detects additional findings in 1/2 pts with core bx-proven DCIS, resulting in changes in MGMT for over 1/3 pts, reducing the number of operations in 10%. Additional MRI findings are associated with lower rate of successful BCT and higher required TM rate. For each pt for whom an operation is prevented, 2 pts have additional tests. Pts with additional MRI findings are more likely to elect TM. Pts with MGMT altered Additional procedures in 19 pts Pts saved an operation Pts electing mastectomy (TM) post-MRI Pts requiring TM Pts with successful BCT Pts with additional MRI findings (N = 41/86) 32/41 (78%) 28 9/41 (22%) 8/41 (20%) 10/41 (24%) 23/41 (56%) Separate lesions (N = 11) 11 16 0 2 1 8 Index lesion larger (N = 23) 15 5 7 3 8 12 Separate lesion and index lesion larger (N = 4) 3 3 1 2 1 1 MRI mass (N = 2) 2 2 1 0 0 2 Adenopathy (N = 1) 1 2 0 1 0 0 Pts without additional MRI findings (N = 45/86) 0 0 0 0 7/45 (16%) 38/45 (84%) Total (N = 86) 32/86 (37%) 28 9/86 (10%) 8/86 (9%) 17/86 (20%) 61/86 (71%) No significant financial relationships to disclose.

Locoregional recurrence of triple‐negative breast cancer after breast‐conserving surgery and radiation

The results of radiation on the local control of triple receptor-negative breast cancer (negative estrogen [ER], progesterone [PR], and HER-2/neu receptors) was studied. Conservative surgery and radiation were used in 753 patients with T1-T2 breast cancer. Three groups were defined by receptor status: Group 1: ER or PR (+); Group 2: ER and PR (-) but HER-2 (+); and Group 3: triple-negative (TN). Factors analyzed were age, menopausal status, race, stage, tumor size, lymph node status, presentation, grade, extensive in situ disease, margins, and systemic therapy. The primary endpoint was 5-year locoregional recurrence (LRR) isolated or total with distant metastases. ER- and PR-negative patients were statistically significantly more likely to be black, have T2 disease, have tumors detectable on both mammography and physical examination, have grade 3 tumors, and receive chemotherapy. There were no significant differences noted with regard to ER- and PR- patients by HER-2 status. There was a significant difference noted in rates of first distant metastases (3%, 12%, and 7% for Groups 1, 2, and 3, respectively; P = .009). However, the isolated 5-year LRR was not significantly different (2.3%, 4.6%, and 3.2%, respectively; P = .36) between the 3 groups. Patients with TN breast cancer do not appear to be at a significantly increased risk for isolated LRR at 5 years and therefore remain appropriate candidates for breast conservation.

Breast cancer radiotherapy: controversies and prospectives

WBI takes 5–7 weeks, with attendant costs and inconveniences. This represents a significant hardship to certain subsets of patients and leads to disparity in breast cancer treatment. Obstacles such as inability to find an X-ray telescope (XRT) center close to home, difficulty in finding transportation to and from a center, lack of family support, and extreme age and/or physical handicap prevent some patients from electing to enter a 6-week course of WBI. Results from the breast-conserving therapy (BCT) trials suggest that up to 86% of the risk for ipsilateral breast cancer recurrence resides in close proximity to the original tumor site. This leads investigators to consider the role of an accelerated and more tumor bed-focused course of radiotherapy. APBI involves the treatment of a limited volume of breast tissue with a dose of irradiation per fraction increased and the treatment time course decreased. The goal is to deliver a dose of irradiation to a limited volume in less time, that is equivalent to the clinical outcome of the conventional 6-week treatment. 8 The importance of proper patient selection cannot be over-stressed when discussing the efficacy of APBI. This includes early stage breast cancer as determined by tumor size less than 2–3 cm, node-negative disease, age of patients more than 45–50 years, and tumor-free margins. 9,10 Additional criteria under study include features such as lobular histology, presence of extensive intraductal component (EIC), lymphvascular invasion, tumor grade and limited node-positive disease. When the tumor histology demonstrates a higher risk for multicentric disease and thus a higher rate for non-tumor bed cancer recurrence, the patients should not be