Prior Breast Cancer Treatment Research Articles

Trimodality Therapy Improves Disease Control in Radiation-Associated Angiosarcoma of the Breast.

To evaluate the impact of trimodality treatment versus monotherapy or dual therapy for radiation-associated angiosarcoma of the breast (RAASB) after prior breast cancer treatment. With Institutional Review Board approval, we identified patients diagnosed with RAASB and abstracted data on disease presentation, treatment, and oncologic outcomes. Trimodality therapy included (i) taxane induction, (ii) concurrent taxane/radiation, and then (iii) surgical resection with wide margins. A total of 38 patients (median age 69 years) met inclusion criteria. Sixteen received trimodality therapy and 22 monotherapy/dual therapy. Skin involvement and disease extent were similar in both groups. All trimodality patients required reconstructive procedures for wound closure/coverage, compared with 48% of monotherapy/dual therapy patients (P < 0.001). Twelve of 16 (75%) patients receiving trimodality therapy had a pathologic complete response (pCR). With median follow-up of 5.6 years, none had local recurrence, 1 patient (6%) had distant recurrence, and no patients died. Among 22 patients in the monotherapy/dual therapy group, 10 (45%) had local recurrence, 8 (36%) had distant recurrence, and 7 (32%) died of disease. Trimodality therapy demonstrated significantly better 5-year recurrence-free survival [RFS; 93.8% vs. 42.9%; P = 0.004; HR, 7.6 (95% confidence interval, CI: 1.3-44.2)]. Combining all patients with RAASB regardless of treatment, local recurrence was associated with subsequent distant recurrence (HR, 9.0; P = 0.002); distant recurrence developed in 3 of 28 (11%) patients without local recurrence compared with 6 of 10 (60%) with local recurrence. The trimodality group had more surgical complications that required reoperation or prolonged healing. Trimodality therapy for RAASB was more toxic but is promising, with a high rate of pCR, durable local control, and improved RFS.

Are Diagnostic Computed Tomography Chest Scans Sufficient for Detecting Supraclavicular in Initial Breast Cancer Staging?

<h3>Purpose/Objective(s)</h3> Initial staging workup strategies for locally advanced or suspected stage IV breast cancer can include computed tomography (CT) of the chest, abdomen, pelvis (CAP) and bone scan or, alternatively, a whole-body positron emission tomography/computed tomography (PET/CT). Variations in intravenous contrast injection site and bolus timing, arm positioning, and acquisition techniques on a CT chest scan could limit visualization of supraclavicular (SCV) and supracricoid cervical lymph nodes, which are critical for staging, prognosis, and treatment recommendations. The study's purpose is to determine whether there is a difference between the incidences of SCV and cervical lymphadenopathy detected on staging CT CAP versus PET/CT scans. <h3>Materials/Methods</h3> The records of consecutive newly diagnosed breast cancer patients who received initial staging scans at a single institution from 2012 to 2017 were reviewed in a HIPAA compliant, institutional review board-approved study. De-identified information was reviewed for inclusion: new breast cancer diagnosis, >18 years old, and availability of staging. Exclusion criteria were prior breast cancer treatment, re-staging for known recurrence, and nondiagnostic imaging examinations. Radiology reports were searched for SCV and cervical lymphadenopathy to determine the incidence detected by each imaging modality. A board certified neuroradiologist reviewed and characterized scans that noted cervical or SCV lymphadenopathy. <h3>Results</h3> The initial search resulted in 3,126 PET/CT and 631 CT CAP scans with 588 patients fulfilling the inclusion criteria. PET/CT scans had been performed in 539 patients and 49 received CT CAP and bone scans. The two groups were well matched by stage (Table 1). Metastatic cervical lymphadenopathy was detected by PET-CT in 50 patients (7.9%) versus two (3.7%) with CT CAP. Out of the 50 patients who had cervical lymphadenopathy detected by PET-CT, 30 (60%) had metastatic cervical lymphadenopathy above the level of the lung apex, the typical upper extent of a CT chest field of view. Although 25 (50%) patients had additional areas of distant metastatic disease, cervical lymphadenopathy above the thoracic inlet was the only site of distant metastasis for 13 patients (26%), and would not have been detectable by CT CAP. <h3>Conclusion</h3> PET/CT detected more cervical and SCV lymphadenopathy than CT CAP in initial staging scans for breast cancer, with 60% of those detected on PET/CTs in areas that would have been occult on standard CT chest scans. Such nodal involvement constituted the only site of distant metastatic disease in 26% of the patients. Thus, dedicated CT neck imaging may be a reasonable addition to CT CAP as an initial staging strategy to determine accurate staging and radiation treatment field volumes and borders.

Concordance between core needle biopsy and surgical excision specimens for Ki-67 in breast cancer - a systematic review of the literature.

The biomarkers oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are routinely measured in patients with breast cancer with international consensus on how they should be interpreted. There is evidence to support use of other biomarkers to give more detailed predictive and prognostic information. Ki-67 is one example, and measures the proliferative activity of cancer cells. It is important that this can be performed at diagnosis of breast cancer for patients who do not have initial surgical treatment (mainly older women) and those receiving neoadjuvant therapies. A systematic review was performed to assess concordance of measurement of Ki-67 between core needle biopsy (CNB) samples and surgical excision (SE) samples in patients with invasive breast cancer. MEDLINE and Embase databases were searched. Studies were eligible if performed within the last 10 years; included quantitative measurement of Ki-67 in both CNB and SE samples with no prior breast cancer treatment; measured concordance between two samples; and had full text available. A total of 22 studies, including 5982 paired CNB and SE samples on which Ki-67 was measured, were appraised. Overall, there appeared to be concordance; however, reliability was unclear. Where given, the Cohen's kappa coefficient (κ) of correlation between samples ranged from 0.261 to 0.712. The concordance rate between CNB and SE where measured as a percentage had a range from 70.3 to 92.7% CONCLUSIONS: Assessment of level of concordance of Ki-67 between CNB and SE samples is hampered by different methodologies. International consensus on Ki-67 measurement is urgently needed.

Therapy-Related Acute Lymphoblastic Leukemia/Lymphoma in the Elderly

IntroductionTherapy-related ALL (t-ALL) is a rare entity. It was recently estimated to occur in about 4.7%-6.9% of adult ALL cases and has been associated with a worse prognosis(Aldoss et al ., 2017; Abdulwahab et al ., 2012). However, these studies included very few patients over the age of 60. Since t-ALL specifically in the elderly has never been described, we sought to characterize its clinical features and treatment outcomes.MethodsAfter IRB approval, we performed a retrospective study of patients (pts) ≥60 years old diagnosed with ALL from 2000-2017 at Mayo Clinic Rochester, Arizona, and Florida. We included pts who received known leukemogenic chemotherapy prior to being diagnosed with ALL. We excluded pts with malignancies who were not exposed to leukemogenic chemotherapy. We also excluded pts diagnosed with chronic myeloid leukemia (CML) with blast crisis. Moreover, we excluded pts treated with radiation therapy other than to the whole pelvic region. Statistical analysis was performed using JMP 10.0 software.ResultsBaseline characteristicsOut of 124 consecutive pts with elderly ALL, we identified 20 (16%) pts who fit our inclusion criteria. 16 (80%) were female. The median latent time to developing ALL was 9.25 years (range 0.26-28.67). The median time of follow-up was 12.6 months (range 0.9-63.2). 11 (55%) were deceased at the time of follow-up: 3 deaths related to disease, 6 from infection or other causes, and 2 unknown.Of the 20 pts with t-ALL, 13 (65%) had been treated for hematological malignancies prior to ALL, which included multiple myeloma (3), acute myeloid leukemia in remission (2), diffuse large B-cell lymphoma (2), myelofibrosis (2), myelodysplastic syndrome (1), MALT lymphoma (1), hairy cell leukemia (1), chronic lymphocytic leukemia (1), and light-chain (AL) amyloidosis (1). Additionally, 6 pts had prior treatment for breast cancer; 1 of these was the pt who also had AL amyloidosis. Finally, 1 pt had a history of receiving cyclophosphamide for bronchiolitis obliterans with organizing pneumonia and myositis.Median age at time of ALL diagnosis was 67 (60-82). 19 (95%) had B-cell ALL, of which 5 (26%) were positive for the Philadelphia chromosome. Only 1 (5%) pt had T-cell ALL.Cytogenetics and FISH studies18 pts had available cytogenetic data at time of diagnosis. 8 (44%) had complex cytogenetics (≥5 abnormalities), 7 (39%) had a monosomal karyotype, 4 (22%) were hyperdiploid, 2 (11%) were hypodiploid, 1 (6%) was a mixture of hyper- and hypo-diploid. Furthermore, FISH analysis was available in 10 pts: 3 had CDKN2A deletion, 2 had a duplication of 1q, 2 had a TCF3-PBX1 translocation, 1 had a MLL rearrangement, and 1 had a deletion of IKZF1 .Treatment and Outcomes15/20 (75%) underwent induction chemotherapy. 6 of them received Hyper-CVAD. The other 9 received various regimens, including asparaginase-based chemotherapy in 6 (67%). 13 (87%) had a complete remission (CR/CRi), within a median time of 32 days (range 19-128). 1 (7%) had primary refractory disease. The other 5 (25%) pts chose palliative treatment up-front; this included chemotherapy (e.g. vincristine and steroids), tyrosine kinase inhibitors, or hospice. 3 (60%) of these pts got into CR.Of the 16 total pts who achieved CR, 5 (31%) relapsed within a median time of 20.67 months (range 9-22.3). All of them were treated with salvage chemotherapy. Median survival after relapse was 4.8 months (range 0.1-42.2). Overall, 7/20 (35%) underwent allogeneic HSCT; all were in CR1. Median survival after HSCT was not reached (IQR 7.6-NR). Only 2 (29%) relapsed after HSCT within a median time of 6.4 months (range 3.1-9.6).The median overall survival (mOS) in patients with t-ALL was 13.83 months (interquartile range [IQR] 11.73-not reached), which was not significantly different (P=0.9935) from elderly patients without t-ALL, who had a mOS of 20.93 months (IQR 8.73-56.63) (Figure 1).ConclusionsTherapy-related ALL (t-ALL) seems to be relatively more common in the elderly compared to younger adults, with an incidence of 16% in our elderly ALL cohort. Almost all cases were B-cell ALL. In addition, MLL rearrangements appeared to be less frequent in our elderly cohort (7%), in contrast to what has been reported in younger adults (25-35%). Moreover, the overall survival in elderly t-ALL was not significantly different compared to elderly ALL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

P1361Impact of radiation/chemotherapy for breast cancer on the electroanatomic features in patients receiving catheter ablation for left atrial arrhythmia

Abstract Background Atrial fibrillation (AF) is a common cardiac arrhythmia and catheter ablation a viable treatment option for patients with AF. Extensive left atrial (LA) scars, frequently seen in patients with persistent AF, can limit its efficacy. Radiation for breast cancer treatment is known to have serious long-term effects (e.g. fibrosis) on the targeted tissue. At the same time, chemotherapy often leads to organ dysfunction. We sought to examine the effects of radiation and chemotherapy on the electroanatomic features of the LA in patients who received catheter ablation for left atrial arrhythmias with prior breast cancer treatment. Methods and Results We compared 38 patients (mean age 68.4 ± 7.1 years) who underwent catheter ablation for LA arrhythmia and had a previous diagnosis of breast cancer with 38 patients (mean age 65.4 ± 7.3 years) without breast cancer who formed our control group. LA scar area, as well as its distribution was measured during the electrophysiology (EP) study and graded according to the Utah classification. The existence of LA scarring did not differ significantly between both groups (71.1% vs. 76.3%, p = 0.602). LA scar area (excluding PVs) was 107.5cm2 ± 19.0cm2 in the breast cancer group compared to 110.1cm2 ± 18.5cm2 in the control group (p = 0.536). The distribution of the scar area revealed no significant difference between both groups, however an involvement of the anterior wall was common (65.8% vs. 73.7%; p = 0.454). We further investigated whether the location of breast cancer had an impact on the LA scar development of the patients in our study cohort. Here, we found no significant difference in the amount of LA scarring when comparing patients with left-sided breast cancer to patients with right-sided breast cancer (66.7% vs. 73.9%). In a sub-analysis patients with breast cancer and persistent AF showed a non-significant trend towards greater LA scar areas (17.4cm2 vs. 6.8cm2) in comparison to patients of the control group with similar LA volumes. The patient’s age (&amp;gt;65 years) was the only independent predictor for greater LA scarring we could identify. Neither former radiotherapy, nor chemotherapy showed a positive correlation with greater LA scarring. Conclusion There is no change in the distribution as well as an increase of the extent of LA scars after thoracic irradiation and/or chemotherapy. A trend towards greater LA scar areas was seen in patients with breast cancer and persistent AF. The patient’s age was identified as an independent predictor for LA scar development.

The impact of bilateral salpingo-oophorectomy on sexuality and quality of life in women with breast cancer.

To compare sexual function and quality of life (QoL) in breast cancer survivors with and without a history of bilateral salpingo-oophorectomy (BSO). A cross-sectional study of breast cancer survivors treated at a tertiary referral hospital in Western Australia. The Female Sexual Function Index was used to determine rates of female sexual dysfunction (FSD) and hypoactive sexual desire disorder (HSDD). Participants also completed the Relationship Assessment Scale, Menopause-specific quality of life questionnaire and Short Form Health Survey-36. A total of 427 women were invited to participate: 119 had undergone BSO and 308 were controls with at least one ovary remaining. A total of 172 women participated (overall response rate 40.3%), consisting of 76 women in the BSO group (response rate 63.9%) and 96 women with at least one ovary remaining (response rate 31.2%). There was no difference in FSD between the two groups: 63/76 (82.9%) women who had undergone BSO had FSD compared to 75/96 (78.1%) controls (p = 0.458). No difference in HSDD was observed (p = 0.084) between the BSO group 70/76 (96.0%) and the controls 96/96 (100%). Women who had undergone BSO had lower general health scores compared to the control group (p = 0.034). Both groups had similar energy levels, emotional well-being, pain scores, physical functioning levels and social functioning levels. In this study, women with prior treatment for breast cancer had high levels of FSD and HSDD, irrespective of whether they had undergone BSO. Both groups reported similar sexual function scores and QoL.

An Evaluation of Safety and Patient Outcomes for Hand Surgery following Prior Breast Cancer Treatment: Establishing New Recommendations in Lymphedema: Correction.

An Evaluation of Safety and Patient Outcomes for Hand Surgery following Prior Breast Cancer Treatment: Establishing New Recommendations in Lymphedema: Correction.

Abstract P1-18-11: Cardiac events in patients with HER2-positive metastatic breast cancer who have low left ventricular ejection fraction prior to initiating treatment with ado-trastuzumab emtansine: A retrospective cohort study using electronic health record data

Abstract Background Cardiac events, including left ventricular ejection fraction (LVEF) decrease and congestive heart failure (CHF), are known risks with HER2-targeted antibody-based therapies. Patients with an LVEF of &amp;lt;50% are typically excluded from clinical trials, including ado-trastuzumab emtansine (T-DM1; Kadcyla®) trials; therefore, this study describes patients with an LVEF of 40-49% prior to initiation of treatment with T-DM1 and evaluates the risk of cardiac events. Methods Patients with HER2-positive metastatic breast cancer treated between Jan 1, 2013 and May 31, 2018 were included from the de-identified US-based Flatiron Health electronic health record-derived database. Patients initiating T-DM1 and with a recent LVEF value of 40-49% up to 60 days prior to treatment were included. Patient baseline characteristics (including cardiac history) were described, and the risk of an LVEF drop of &amp;gt;10% points, CHF, and other cardiac events during treatment, and the 84 days following treatment discontinuation, were examined. Results Of approximately 2000 patients with metastatic breast cancer initiating T-DM1 in the database, 32 (1.6%) had an LVEF measurement of 40-49% at baseline (as defined above). These patients had a median age of 64.5 years, median body mass index of 26.1 kg/m2, and 65.6% were white. Median T-DM1 treatment duration was 4.6 months. Cardiac history included prior breast cancer treatment discontinuation due to cardiotoxicity (62.5%), CHF signs and symptoms (34.4%), CHF (28.1%), and prior cardiac hospitalization (18.8%). LVEF monitoring was conducted during treatment for 81.0% of patients who had &amp;gt;2 months of T-DM1 treatment. An LVEF drop of &amp;gt;10% points occurred in four patients (12.5%); CHF events, in five patients (15.6%). Incidence rates were 34.4 and 8.5 per 100 person-years, respectively. These nine events occurred in seven patients, six of whom had relevant cardiac history events recorded in their electronic health record at baseline. CHF signs and symptoms were reported in nine patients (28.1%; 50.5 per 100 person-years) and cardiac tachyarrhythmia in one patient (3.1%; 5.1 per 100 person-years). In a sensitivity analysis that comprised 35 additional patients (N=67) with an LVEF of 40-50% (including overlapping LVEF ranges), the following additional events were recorded: CHF (1); cardiac tachyarrhythmia (1), and CHF signs and symptoms (6). Conclusion A small proportion of patients initiate T-DM1 with low LVEF. The risk of cardiac events observed appears to be consistent with the population profile presenting a cardiac history. The decision for physicians to prescribe T-DM1 in patients with low LVEF should be made in the context of the benefit-risk consideration for cardiac events and the availability of alternative treatment. Citation Format: Thibaut Sanglier, Jinjoo Shim, Harry Liu, Chunyan Song, Melanie Smitt, Evelyn M Flahavan. Cardiac events in patients with HER2-positive metastatic breast cancer who have low left ventricular ejection fraction prior to initiating treatment with ado-trastuzumab emtansine: A retrospective cohort study using electronic health record data [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 P1-18-11.

An Evaluation of Safety and Patient Outcomes for Hand Surgery following Prior Breast Cancer Treatment: Establishing New Recommendations in Lymphedema.

Injuries to the upper extremity lymphatic system from cancer may require measures to prevent secondary lymphedema. Guidelines were established relating to the use of tourniquet and elective hand and upper extremity surgery. However, reports in the setting of hand surgery have indicated that prior guidelines may not be protective to the patient. The study systematically reviewed the current literature evaluating elective hand surgery in breast cancer patients. The authors evaluated the risk of complications, including new or worsening lymphedema and infection. One hundred ninety-eight abstracts were identified, and a bibliographic review was performed. Nine studies pertained to our subject, and four were included for final review. All studies included patients with prior breast cancer treatment involving breast surgery and axillary lymph node dissection. Pneumatic tourniquets were used during nearly all operations. Patients without presurgery ipsilateral lymphedema had a 2.7 percent incidence of developing new lymphedema and a 0.7 percent rate of postoperative infection. Patients with presurgery lymphedema had a 11.1 percent incidence of worsening lymphedema and a 16.7 percent rate of infection. However, all cases of new or exacerbated lymphedema resolved within 3 months. Tourniquet use was not found to increase rates of lymphedema. Based on the available evidence, there is no increased risk of complications for elective hand surgery in patients with prior breast cancer treatment. Breast cancer patients with preexisting ipsilateral lymphedema carry slightly increased risk of postoperative infection and worsening lymphedema. It is the authors' opinion and recommendation that elective hand surgery with a tourniquet is not a contradiction in patients who have received previous breast cancer treatments.

Discussion: An Evaluation of Safety and Patient Outcomes for Hand Surgery following Prior Breast Cancer Treatment: Establishing New Recommendations in Lymphedema.

Discussion: An Evaluation of Safety and Patient Outcomes for Hand Surgery following Prior Breast Cancer Treatment: Establishing New Recommendations in Lymphedema.

Abstract OT2-03-01: Multicenter study to standardize and evaluate the efficacy of radiofrequency ablation therapy for early breast cancer (RAFAELO study)

Abstract Background: Early-stage breast cancer is increasingly detected by screening mammography, and we aim to establish radiofrequency ablation therapy (RFA) as a minimally invasive, cost-efficient, and cosmetically acceptable local treatment. In our Phase I study, localized tumors with a maximum diameter of 2 cm, preoperatively diagnosed by imaging and histopathology, were treated with RFA. A 90% complete ablation rate was confirmed histopathologically. Our phase II multicenter study of RFA without resection for early breast cancer will evaluate the long-term safety and efficacy of RFA as well as its cosmetic results, which are a perceived advantage of this technique. Trial design: This study is a Phase III, single-arm, multicenter study being conducted with the participation of 11 hospitals. In our experimental therapy, a radiofrequency electrode needle is inserted through the skin into the breast lesion under imaging guidance, followed by thermal ablation with radiofrequency waves. RFA will be conducted under general anesthesia. The Cool-tip™ RF Ablation Single Electrode Kit (Medtronic, CO, USA) will be used to standardize the evaluation of the ablation effect. After RFA, all patients will receive radiotherapy and systemic therapy according to the ER, HER2, tumor grade, and lymph node status of the primary tumor. Residual lesions after RFA will be assessed approximately 3 months after radiotherapy using imaging and pathological studies. All patients will undergo vacuum-assisted biopsy regardless of imaging results. If specimens show viable tumor tissue, additional excision will be performed. Follow-up evaluation for residual tumor, including clinical breast examination and diagnostic imaging (ultrasound, MRI, and mammography), will be performed yearly after RFA. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000012429. Eligibility criteria: Early breast cancer patients, who are lack of prior treatment for breast cancer and histologically confirmed ductal carcinoma with a single localized tumor of 1.5 cm or less in the greatest dimension and clinically node negative on preoperative imaging. Specific Aims: The primary endpoint is 5-year ipsilateral breast tumor recurrence(IBTR) rate, and the secondary endpoints are residual lesion rate, overall survival, DFS, and adverse events of RFA. Statistical methods: The IBTR rate should be similar to that with standard treatment (BCS). However, the IBTR after RFA alone may be higher by up to 10% than in the NSABP-B06 study; therefore the 5-year IBTR rate is estimated to be 6.3%. We calculated the required sample size based on the following assumptions: a clinically acceptable 5-year local recurrence-free survival rate of 90%, a one-sided significance level of 5% (alpha = 0.1, 2-sided), and power of 80% (beta = 0.2). Taking into account a drop-out rate of 10%, approximately 372 patients will be enrolled in the study. Present accrual and target accrual: The trial was activated in August 2013, with a total of 372 patients enrolled by the end of June 2018. Citation Format: Kinosita T, Takahashi M, Fujisawa T, Yamamoto N, Doihara H, Ohtani S, Futamura M, Takahashi M, Aogi K, Hojo T, Yoshida M, Shiino S, Tsuda H. Multicenter study to standardize and evaluate the efficacy of radiofrequency ablation therapy for early breast cancer (RAFAELO study) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-03-01.

Abstract PD2-13: Benefits to breast screening beyond mortality reduction

Abstract Background The value of population-based mammographic screening has been questioned by those who believe that the reduction in mortality from earlier diagnosis is outweighed by harms including overdiagnosis and overtreatment. Much of these commentaries assume that all Early-Stage Breast Cancer (ESBC) is treated the same way after diagnosis; with extensive therapies including surgery, radiotherapy and chemotherapy being standard. Intensity of treatment received is rarely mentioned in the debate. We hypothesised that those diagnosed through a screening program (Active Screeners (AS)) would receive less extensive surgical treatment and less intense adjuvant therapies than those not recently screened (NRS). If demonstrated, these differences would form an important component of the debate over the role of mammographic screening. Methods Retrospective analysis of a consecutive cohort of female patients aged 50-69 and managed for ESBC (invasive or DCIS) during 2007-2013 within a large metropolitan Breast Service, diagnosed either via a population screening program (AS) or outside of the program (NRS). Data on patient characteristics, symptoms, mode of detection, tumour pathology, surgical intervention and adjuvant treatment recommendations were derived from prospectively collected Multi-Disciplinary Meeting (MDM) records. Patients with metastatic disease or prior treatment for breast cancer were excluded. Results 791 cases were identified (569 with screen-detected cancer, 53 with interval cancers and 169 cancers diagnosed in women not recently screened). Invasive cancers in the AS group were much smaller than in the NRS group – mean 17mm versus 26mm. The AS group had lower grade invasive cancer – grade 1, 2 and 3 were 27%, 42%, 31% - compared with 10%, 39% and 52% in the NRS group. The AS group were more likely to have ER+ve cancers (88% vs 80%) and less likely to have nodal involvement (26% vs 48%). For invasive breast cancer, the NRS group were more than twice as likely to undergo mastectomy than cancers in the AS group (35% vs 16%). Axillary dissections were more common in the NRS than the AS group (43% vs 19%). Adjuvant chemotherapy was recommended more frequently for the NRS group compared to the AS group (65% vs 37%), as was post mastectomy radiotherapy (58% vs 39%). Endocrine therapy was less often recommended to the NRS group (86% versus 77%). Conclusion Women diagnosed with early stage breast cancer who are participating in a population based screening program are less likely to receive mastectomy and/or axillary dissection, less likely to receive adjuvant chemotherapy and less likely to receive post-mastectomy radiotherapy. These differences in treatment intensity should be considered in the debate surrounding mammographic screening. Citation Format: Elder KJ, Nickson C, Cooke S, Machalek D, Rose A, Mou A, Collins JP, Park A, De Boer R, Phillips C, Pridmore V, Farrugia H, Mann GB. Benefits to breast screening beyond mortality reduction [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 PD2-13.

Heterogeneity Factor Analysis of Studies Evaluating the Effect of Tai Chi on Improving the Overall Quality of Life in Patients with Breast Cancer

Background: In the case of large heterogeneity, the data combination of randomized controlled trials will lead to the decrease of the reliability of systematic review and meta analysis, so we conducted the present study. Objectives: To explore sources of heterogeneity in studies on Tai Chi Chuan (TCC) as a complementary and alternative method for managing the overall quality of life of postoperative breast cancer patients. Methods: Randomized controlled trials were searched for in PubMed, EMBASE, Web of Science and the Cochrane Library through August 2017. The Cochrane Handbook 5.2 standards and Stata software version 10.0 were adopted for evaluating the quality of the included studies and the data was analyzed on overall quality of life of TCC. A separate univariate meta-regression analysis was performed on the study duration, sample size, cancer staging, prior breast cancer treatment, different types of TCC intervention group, different types of control group, intervention duration, mean age, and ethnicity to detect important factors leading to heterogeneity. Results: Significant heterogeneity was present in the included studies that used TCC to improve the overall quality of life of postoperative breast cancer patients from the retrieved literature (P < 0.05). The univariate meta-regression analysis indicated that the source of heterogeneity was not apparent in the analyzed factors within or between studies. Conclusions: A normative approach in studies evaluating the use of TCC for improving the overall quality of life of postoperative breast cancer patients was not sufficiently explored in the existing randomized controlled trials (RCTs). An insufficient number of RCTs in this field may be the reason that the effect size had unclear clinical significance. The existing evidence provided limited judgment on sources of heterogeneity between studies evaluating the use of TCC for improving overall quality of life in postoperative breast cancer patients.

Use of prophylactic postoperative antibiotics during surgical drain presence following mastectomy.

National guidelines recommend one dose of perioperative antibiotics for breast surgery and discourage postoperative continuation. However, reported skin and soft tissue infection (SSI) rates after mastectomy range from 1-26%, higher than expected for clean cases. Utility of routine or selective postoperative antibiotic use for duration of drain presence following mastectomy remains uncertain. This study included all female patients who underwent mastectomy without reconstruction at our institution between 2005 and 2012. SSI was defined using CDC criteria or clinical diagnosis of cellulitis. Information on risk factors for infection (age, body mass index [BMI], smoking status, diabetes, steroid use), prior breast cancer treatment, drain duration, and antibiotic use was abstracted from medical records. Multivariable logistic regression was used to assess the association between postoperative antibiotic use and the occurrence of SSI, adjusting for concurrent risk factors. Among 480 patients undergoing mastectomy without reconstruction, 425 had sufficient documentation for analysis. Of these, 268 were prescribed antibiotics (63%) at hospital discharge. An overall SSI rate of 7.3% was observed, with 14% of patients without postoperative antibiotics developing SSI compared with 3.4% with antibiotics (p<0.0001). Factors independently associated with SSI were smoking and advancing age. Diabetes, steroid use, BMI, prior breast surgery, neoadjuvant chemotherapy, prior radiation, concomitant axillary surgery, and drain duration were not associated with increased SSI rates. SSI rates among patients who did and did not receive postoperative antibiotics after mastectomy were significantly different, particularly among smokers and women of advanced age. These patient subgroups may warrant special consideration for postoperative antibiotics.

Role of Elective Hand Surgery and Tourniquet Use in Patients With Prior Breast Cancer Treatment

Role of Elective Hand Surgery and Tourniquet Use in Patients With Prior Breast Cancer Treatment

PD07-04: Lapatinib vs Trastuzumab in Combination with Standard EC-D Chemotherapy in the Neaodjuvant Treatment of HER2+ Patients. Results from the GEICAM 2006–14 Phase II Randomized Trial.

Abstract Background: The addition of trastuzumab (T) to neoadjuvant chemotherapy increases pCR rate in patients with HER2 + breast cancer. Lapatinib (L) in combination with chemotherapy is also an active drug in breast cancer patients. This study investigates the efficacy of trastuzumab or lapatinib added to chemotherapy in the neoadjuvant setting. Methods: Patients (Pt) with tumors greater than 2 cm (or less with positive axilla) and HER2+ (Herceptest 3+ or 2+ with FISH+) that have not received any prior treatment for breast cancer were recruited. Pts were randomized to receive epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 × 4 cycles (cy) followed by docetaxel 100 mg/m2 (with growth colony stimulating factor support) plus either T 8 mg/kg loading dose and then 6 mg/Kg intravenous (EC-DT) or L 1250 mg orally (EC-DL). Patients were stratified according to tumor size (T1-2 vs T3-4), and estrogen receptor status (positive vs negative). The primary end-point was pathological complete response (pCR) in the breast measured by Miller and Payne criteria. Secondary end-points were clinical response (by imaging test), toxicity and correlation between pCR and tumor biomarkers. Results: From February-09 to October-10, 102 pts were randomized (50 EC-DT, 52 EC-DL). Pts characteristics were well balanced between arms. Median age was 48 years (30-79), 56% of pts were premenopausal, 7% grade I, 45% grade III. 14/59/12/15% were T1/T2/T3/T4 and 69% N+. 58% were estrogen receptor positive and 44% progesterone receptor positive. Three patients were FISH negative after central assessment and were not considered evaluable for efficacy. pCR rate in the breast was 52% (95% CI: 38–66) for EC-DT and 25% (95% CI: 13.5−37.5) for EC-DL (p-value=0.0065). pCR—pN0 was 48% (95% CI: 34–62) for EC-DT and 24% (95% CI: 12 - 35) for EC-DL (p-value=0.01). Clinical response was 77% with EC-DT and 65% with EC-DL (p-value=0.176). Grade III-IV toxicity was similar between arms except for diarrhea that was more frequent in EC-DL 14% than in EC-DT 2% (p-value=0.03); more patients discontinue treatment due to toxicity with EC-DL (1 vs 6; p-value=0.055). Conclusions: Our study shows that EC-DT was more efficacious and less toxic than EC-DL in the neoadjuvant treatment of HER2+ pts. Biomarker profiling in the tumors, including activation levels of tyrosine-kinase receptors, signaling pathways and surrogate markers (proliferation and apoptosis) is ongoing; their correlation with pCR will be presented at the meeting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD07-04.

Role of Elective Hand Surgery and Tourniquet Use in Patients With Prior Breast Cancer Treatment

Role of Elective Hand Surgery and Tourniquet Use in Patients With Prior Breast Cancer Treatment

Breast cancer and bone mineral density: The Marburg Breast Cancer and Osteoporosis Trial (MABOT II)

Objectives The current case–control study is the first to examine the relationship between bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasonometry (QUS) in pre- as well as postmenopausal women with breast cancer compared to healthy matched controls.Methods Among 1422 women (premenopausal, n = 238, postmenopausal, n = 1184), BMD and QUS were measured. In total, 541 of the women had an incident diagnosis of breast cancer (122 premenopausal, 419 postmenopausal) without prior breast cancer treatment. Because of significant intergroup differences in multiple risk factors, a matched-pair analysis (88 premenopausal and 402 postmenopausal women with and without breast cancer) was performed. Additionally, a multiple linear regression analysis was undertaken, odds ratios were determined and subjects grouped according to quartiles of DXA and QUS results.Results DXA results (except the L1–L4 Z-score) were significantly higher in postmenopausal women with breast cancer even after a matched-pair analysis was performed (p < 0.05). In premenopausal women, we observed no significant differences in DXA results between the groups. QUS results in pre- and postmenopausal women with breast cancer were significantly higher compared with their matched controls (p < 0.001 for all, except for speed of sound in premenopausal patients, p < 0.05). Odds ratios for breast cancer risk in the second, third and fourth quartiles compared with the lowest quartile were significantly different for a number of variables.Conclusions Our results showed significantly higher BMD irrespective of the method and site of measurement in postmenopausal women with breast cancer compared to controls, even after matching for possible confounders for the first time.

Frequency of Certain Established Risk Factors in Soft Tissue Sarcomas in Adults: A Prospective Descriptive Study of 658 Cases

Soft tissue sarcomas are rare tumours with infrequent identified aetiological factors. Several genetic syndromes as well as previous radiation therapy and/or chronic lymphoedema have been suspected to predispose to some soft tissue sarcomas. Between January 1997 and September 2005, we carried out a prospective descriptive study to estimate the frequency of some particular etiological factors among 658 patients with soft tissue sarcomas. Sarcomas associated with a clinically identified genetic disease represent 2.8% out of all cases (95%CI: 1.5–3.8%). Most of these cases (14/19) are related to Recklinghausen neurofibromatosis. Radiation-induced sarcomas represent 3.3% out of all cases (95%CI: 1.7–5.1%). Most of these cases (9/22) are related to prior breast cancer treatment. We had observed only 1 case of Stewart-Treves syndrome. Liposarcoma, the most frequent histological subtype observed, is not associated with any particular aetiological entity. Finally, most of the adult soft tissue sarcomas are not related to any classical clinically identified genetic disease or previous radiation therapy and/or chronic lymphoedema risk factors. Frequency of underlying genetic syndrome which may predispose to soft tissue sarcomas could be higher than previously reported.

Association between clinical characteristics and risk‐reduction interventions in women who underwent BRCA1 and BRCA2 testing

Women who are at increased risk for breast and ovarian cancers, especially BRCA1 and BRCA2 mutation carriers, face a myriad of risk-reduction options, including increased surveillance, chemoprevention, prophylactic oophorectomy, and prophylactic mastectomy. However, little is known about which clinical, demographic, or cancer-related factors are associated with risk-reduction interventions. The authors conducted a retrospective review of records for 554 women who had undergone testing at The University of Texas M. D. Anderson Cancer Center between 2000 and 2006 for deleterious BRCA1 and BRCA2 gene mutations. Data were collected on the risk-reduction interventions these women adopted after they underwent genetic testing. These data were tested for associations with demographic and clinical characteristics. Among the 554 women who underwent genetic testing for BRCA mutation, 78 were found to have a deleterious mutation in the BRCA1 gene, and 54 had a mutation in the BRCA 2 gene. Of the 554 women, 85 underwent prophylactic mastectomy, 30 prophylactic oophorectomy, and 52 both surgeries; 387 women opted for surveillance. Women who had BRCA mutations, a history of breast cancer or ductal carcinoma in situ (DCIS), or previous breast biopsies were more likely to have prophylactic surgery. Women with a family history of ovarian cancer were more likely to undergo prophylactic oophorectomy. Women with a personal history of ovarian cancer or advanced breast cancer were more likely to undergo surveillance only. Women with breast cancer who had had a total mastectomy as part of their prior breast cancer treatment underwent prophylactic mastectomy more frequently than women who either had breast-conserving surgery or no history of breast cancer. In multivariate analysis, only positive BRCA mutation carrier status was associated with having had prophylactic surgery. In addition, breast cancer history was significantly associated with prophylactic mastectomy. Women who were BRCA carriers, women who had a history of breast cancer, DCIS, or breast biopsy, or had a family history of ovarian cancer were more likely to have undergone surgery for cancer risk reduction. Women with ovarian cancer or advanced breast cancer were more likely to have undergone surveillance.