Early-stage Primary Breast Cancer Research Articles

Distress, Pain, and Nausea on Postoperative Days 1 and 14 in Women Recovering From Breast-Conserving Surgery: A Repeated-Measures Study.

To determine the incidence and trajectory of distress, pain, and nausea and vomiting at postoperative day (POD) 1 and at POD 14 following breast-conserving surgery. 75 women aged 18 years or older receiving breast-conserving surgery with sentinel lymph node biopsy for treatment of early-stage primary breast cancer at an ambulatory surgery center. This prospective, repeated-measures study assessed distress, pain, and nausea and vomiting using the National Comprehensive Cancer Network Distress Thermometer and Problem List on POD 1 and POD 14. Pain and distress scores were highest on POD 1. The number of women who reported depression increased from POD 1 to POD 14. Thematic analysis revealed that family concerns, fears and worries, and postoperative issues contributed to pain and distress. Women experience pain and distress during recovery at home after breast-conserving surgery. Nurses can use these results to apply evidence-based practice to reduce this symptom burden. Future nursing research should focus on targeted interventions outside of the hospital setting.

Percutaneous ultrasound-guided cryoablation for early-stage primary breast cancer: a follow-up study in Japan

BackgroundUltrasound-guided percutaneous cryoablation (PCA) for early-stage breast cancer (ESBC) can be performed under local anesthesia in an outpatient clinic. This study continues a pilot stage to examine local control, safety, patient quality of life (QoL), satisfaction and cosmetic outcomes of cryoablation for ESBC.MethodsPCA was performed under local anesthesia for patients with primary ESBC, followed by radiation and endocrine therapies. Oncologic outcomes were examined by imaging (mammography, ultrasound, MRI) at baseline and 1, 6, 12, 24, 36, and 60 months post-cryoablation. EQ-VAS, EQ-5D-5L, subjective satisfaction and Moiré topography were used to measure health-related QoL outcomes.ResultsEighteen patients, mean aged 59.0 ± 9.0 years, mean tumor size 9.8 ± 2.3 mm, ER + , PR + (17/18), HER2-, Ki67 < 20% (15/18), underwent PCA and were followed for a mean of 44.3 months. No serious adverse events were reported, and no patients had local recurrence or distant metastasis in the 5-year follow-up. Cosmetic outcomes, satisfaction level, and QoL all improved post-cryoablation. Five-year average reduction rates of the cryolesion long, short, and depth diameters, on US, were 61.3%, 42.3%, and 22.8%, respectively, compared to the 86.2% volume reduction rate on MRI. The correlation coefficient between MRI and US measurement criteria was highest for the long diameter. During follow-up, calcification of the treated area was observed in 13/18 cases.ConclusionCryoablation for ESBC is an effective and safe procedure with excellent cosmetic outcomes and improved QoL. This study contributes to the growing evidence supporting cryoablation as a potential standard treatment for ESBC, given compliance to pre-defined patient selection criteria.

HRD signature and HRD genomic landscape of tumors from 896 patients with early-stage breast cancer (BC).

539 Background: Pathologic mutations in BRCA1, BRCA2 and PALB2 lead to impaired homologous recombination repair (HRR). Cells with defects in HRR are dependent on non-homologous DNA end joining for DNA repair through the poly(ADP-ribose) polymerase (PARP) catalytic activity. PARP inhibitors (olaparib, talazoparib) are FDA-approved therapies that are toxic to tumors with HRR deficiency (HRD) and are recommended as adjuvant therapy in high-risk germline BRCA (g BRCA) positive BC. Despite the clinical implications of HRD, the prevalence of HRR alterations and HRD signature in early-stage primary BC and its association with hormone receptor (HR) status has not been well characterized. Methods: This study used the nationwide (US-based, ~280 US cancer clinics) de-identified Flatiron Health-Foundation Medicine BC clinico-genomic database and included patients (pts) who underwent tissue comprehensive genomic profiling (FoundationOne/FoundationOneCDx) between 2014 and 2022. The analysis included all pts with BC who presented with “early” stage I-III disease), had a primary tissue specimen collected within 3 months of diagnosis, and had a reportable novel scar-based HRD signature (HRDsig). Results: A total of 896 primary BC pts with stage I-III met our inclusion criteria. Of these early BC pts 21% (188/896) were HRDsig+ (stage I: 17% (32/188); stage II: 22% (84/376); and stage III: 22% (72/332)). For early BC pts, high rates of HRDsig+ were seen in g BRCA (87% [34/39]), somatic BRCA (s BRCA, 78% [14/18]), and g PALB2 (71% [5/7]) mutated tumors, with a lower rate seen with other HRR genes [16% (10/63); ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, sPALB2, RAD51B, RAD51C, RAD51D and RAD54L]. HRDsig+ was also detected in 16% (135/832) of BC without g/s BRCA or g PALB2 mutations. BC pts who presented with stage I-III disease has similar prevalence of HRDsig+ when compared to those with stage IV disease (21% [188/896] vs 23% [177/767], p = 0.31), with similar trends in HR+ disease (HR+/HER2+: 7% [4/57] vs 9% [4/45], p = 0.73; and HR+/HER2-: 17% [78/466] vs 18% [82/463], p = 0.73). Conversely, in HR- cohorts, decreased prevalence of HRDsig+ was observed in the stage I-III vs stage IV cohort (HR-/HER2+: 3% [1/38] vs 18% [6/33], p = 0.04; HR-/HER2-: 31% [99/321] vs 38% [83/216], p = 0.08). Conclusions: In this study, HR+/HER2- group was the most common early BC subtype, followed by HR-/HER2-, HR+/HER2+, and HR-/HER2+. This distribution is similar to the SEER study, and closely reflects that of the general population. We observed the expected high rates of HRDsig+ in early-stage BC pts with g/s BRCA or g PALB2 mutations where clinical trial data already support the use of PARP inhibitors for early and advanced disease. Importantly, HRDsig positivity was also seen in 16% of early BC without g/s BRCA or g PALB2, and clinical trials will be needed to determine if these pts could also benefit from HRD directed therapies.

Abstract P3-03-22: Overweight and obesity trends over 5 years in early stage and metastatic breast cancer patients

Abstract Background: Obesity is associated with 25-33% of all breast cancer (BC) cases, and BC survivors with obesity have a 35% higher risk of BC-related death and 41% higher risk of all-cause mortality. We hypothesized that the prevalence of overweight (body mass index [BMI] 25-29.9 kg/m2) and obesity (BMI ≥30) after a diagnosis of early stage or metastatic BC increases, and baseline characteristics may increase risk of weight gain. Methods: We conducted a retrospective chart review of 222 patients with Stage 0-IV BC who newly presented to Johns Hopkins from 2015-2018. Patients were part of the BC Program Quality Improvement Project Database, had 1 chest CT scan within 6 months of initial visit, and at least 1 subsequent CT. Data extracted from the medical record included: demographics, menopausal status, diagnosis date, cancer characteristics/treatment, recurrence/vital status, family history of BC, and tobacco/alcohol use. All BMI measured on patients were collected. Baseline BMI was defined as the closest measurement to BC diagnosis between 1 year prior and 1 month after diagnosis. We estimated time to overweight/obesity from diagnosis using the Kaplan Meier method and compared between subgroups with the log rank test. Patients who were overweight/obese at diagnosis were included in the analysis with an event time of zero. Results: Among 222 patients, 110 patients (50%) had newly diagnosed early-stage BC, 98 (44%) had de-novo or recurrent metastatic BC, and 14 (6.3%) had locally recurrent BC. Most patients were women (98%) and non-Hispanic (93%). Patients identified as White (62%), Black (23%), and Asian (8%). Among 34% with alcohol use, 5% reported ≥8 drinks/week. There were current (6%) and former smokers (34%). Family history of BC was present in 10%. Among those with early-stage primary BC, most were postmenopausal (61%) and received chemotherapy (61%). Hormone receptor (HR)-positive, HER2-positive and triple negative subtypes were 70%, 24% and 19%, respectively. For those with metastatic BC, most were postmenopausal (62%). Hormone receptor (HR)-positive, HER2-positive and triple negative subtypes were 71%, 12% and 24%. At diagnosis, 73% of the whole cohort had BMI ≥25 kg/m2, with the whole cohort and subgroups having mean BMI ≥25 kg/m2. The incidence of elevated BMI increased in all groups and overall, over 5 years (Table 1). Weight gain was significantly associated with premenopausal status (p=0.04). Stage at diagnosis, smoking/alcohol use, receipt of chemotherapy/radiation/endocrine therapy, and subtype were not associated with weight gain. Conclusion: Patients with early stage and metastatic BC have elevated BMI at diagnosis, and this risk increases over 5 years, especially for those who are premenopausal. Further investigation of the implications of these changes is needed. Additionally, while BMI is accessible, it may underestimate body fat in older people and others who have lost muscle, does not identify fat distribution (a major factor in metabolic health risk), and may not be equally valid across gender, race and ethnicities and age groups. We will assess body composition by CT scan and report correlations with BMI and cancer-related outcomes. Prevalence of BMI≥25 kg/m2 in patients with breast cancer at diagnosis and by 1-, 2-, and 5-years after Prevalence of BMI≥25 kg/m2 increased over 5 years post-diagnosis. Premenopausal status was more associated with BMI≥25 kg/m2 versus postmenopausal status. Citation Format: Terrence Tsou, Amanda L. Blackford, Vered Stearns, Jennifer Y. Sheng. Overweight and obesity trends over 5 years in early stage and metastatic breast cancer patients [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 P3-03-22.

Medicaid expansion, chemotherapy delays, and racial disparities among women with early-stage breast cancer.

Medicaid expansion under the Affordable Care Actextends eligibility for participating states and has been associated with improved outcomes by facilitating access to care. Delayed initiation of adjuvant chemotherapy is associated with worse outcomes among patients with early-stage breast cancer (BC). The impact of Medicaid expansion in narrowing delays by race and ethnicity has not been studied, to our knowledge. This was a population-based study using the National Cancer Database. Patients diagnosed with primary early-stage BC between 2007 and 2017 residing in states that underwent Medicaid expansion in January 2014 were included. Time to chemotherapy initiation and proportion of patients experiencing chemotherapy delays (>60 days) were evaluated using difference-in-difference and Cox proportional hazards models in preexpansion and postexpansion periods according to race and ethnicity. A total 100 643 patients were included (63 313 preexpansion and 37 330 postexpansion). After Medicaid expansion, the proportion of patients experiencing chemotherapy initiation delay decreased from 23.4% to 19.4%. The absolute decrease was 3.2, 5.3, 6.4, and 4.8 percentage points (ppt) for Black, Hispanic, White, and Other patients. Compared with White patients, statistically significant adjusted difference-in-differences were observed for Black (-2.1 ppt, 95% confidence interval [CI] = -3.7% to -0.5%) and Hispanic patients (-3.2 ppt, 95% CI = -5.6% to -0.9%). Statistically significant reductions in time to chemotherapy between expansion periods were observed among White patients (adjusted hazard ratio = .11, 95% CI = 1.09 to 1.12) and those belonging to racialized groups (adjusted hazard ratio = 1.14, 95% CI = 1.11 to 1.17). Among patients with early-stage BC, Medicaid expansion was associated with a reduction in racial disparities by decreasing the gap in the proportion of Black and Hispanic patients experiencing delays in adjuvant chemotherapy initiation.

Patient experiences and views on pharmaceutical care during adjuvant endocrine therapy for breast cancer: A qualitative study.

The use of adjuvant endocrine therapy (AET) after primary treatment of hormone receptor-positive breast cancer reduces the risk of recurrence and mortality. However, non-adherence is still common. Limited consideration has been given to how users deal with AET and the role of pharmaceutical care. Therefore, this study aims to obtain insight into the needs and wishes of women using AET regarding pharmaceutical care and eHealth. This is a qualitative explorative study comprising semi-structured interviews (n = 16) and a focus group (n = 5) among women who use or used AET after primary early-stage breast cancer (EBC) treatment using a thematic analysis approach. Three themes emerged from the interviews and focus group: (1) experiences with AET use, (2) experiences with provided information and (3) needs and wishes regarding pharmaceutical care. Most women were highly motivated to use AET and indicated to have received useful information on AET. However, many expressed a strong need for more elaborate tailored and timely provided information on AET. They acknowledged the accessibility of pharmacists but reported that currently, pharmacists are hardly involved in AET care. Several women considered eHealth useful to obtain counselling and reliable information. Women need more comprehensive information and follow-up in primary setting after initial cancer treatments. A more elaborate role for the pharmacy and eHealth/mHealth, especially with regard to counselling on side effects and side effect management, could potentially improve pharmaceutical care.

Cytoplasmic LXR expression is an independent marker of poor prognosis for patients with early stage primary breast cancer

PurposeThe aim of this study was to investigate the expression of liver X receptors α/β (LXR) in primary breast cancer (BC) tissues and to analyze its correlations with clinicopathological parameters including patient survival.MethodsIn a well-characterized cohort of 305 primary BC, subcellular distribution of LXR was evaluated by immunohistochemistry. Correlations with clinicopathological characteristics as well as with patient outcome were analyzed.ResultsLXR was frequently localized in both nuclei and cytoplasms of BC cells, with stronger staining in nuclei. Total and nuclear LXR expression was positively correlated with ER and PR status. Overall survival analysis demonstrated that cytoplasmic LXR was significantly correlated with poor survival and appeared as an independent marker of poor prognosis, in stage I but not in stage II–III tumorsConclusionAltogether, these data suggest that cytoplasmic LXR could be defined as a prognostic marker in early stage primary BC.

Discordance in ER, PR, HER2, and Ki-67 Expression Between Primary and Recurrent/Metastatic Lesions in Patients with Primary Early Stage Breast Cancer and the Clinical Significance: Retrospective Analysis of 75 Cases.

Background: The objective was to explore the discordance in the expression of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 between primary and recurrent/metastatic lesions in patients with early stage breast cancer as well as the prognostic impact. Method: Patients with early-stage primary breast cancer and confirmed recurrence/metastasis at Peking Union Medical College Hospital between January 2005 and August 2018 were screened. The details of discordance in each parameter between primary and recurrent/metastatic lesions and progression were recorded. Regression and survival analysis were applied to determine the association and clinical impact of the discordance. Results: We evaluated 75 patients. The discordance rate of ER, PR, HER2, and Ki-67 expression was 9.3, 14.7, 14.7, and 21.5%, respectively. Additionally, 66.7, 11.8, 14.3, and 0% of patients with Luminal A, Luminal B, HER2, and triple-negative primary tumors presented with a different subtype for the recurrent/metastatic tumors, respectively. No statistical difference in progression-free survival was observed according to the subtype of the recurrent or metastatic breast cancer (p > 0.05). Among 69 patients for whom treatment was adjusted after recurrence or metastasis, 66 patients remained recurrence-free during the follow-up period. Conclusion: For patients with early-stage breast cancer, the ER, PR, HER2, and Ki-67 expression profile for recurrent/metastatic tumors does not always match that of the primary tumor. After adjusting treatment according to the receptor expression in recurrent/metastatic lesions, most patients remained progression-free during the follow-up period.

Preexisting Somatic Mutations of Estrogen Receptor Alpha (ESR1) in Early-Stage Primary Breast Cancer.

BackgroundMore than three-quarters of primary breast cancers are positive for estrogen receptor alpha (ER; encoded by the gene ESR1), the most important factor for directing anti-estrogenic endocrine therapy (ET). Recently, mutations in ESR1 were identified as acquired mechanisms of resistance to ET, found in 12% to 55% of metastatic breast cancers treated previously with ET.MethodsWe analyzed 3217 population-based invasive primary (nonmetastatic) breast cancers (within the SCAN-B study, ClinicalTrials.gov NCT02306096), sampled from initial diagnosis prior to any treatment, for the presence of ESR1 mutations using RNA sequencing. Mutations were verified by droplet digital polymerase chain reaction on tumor and normal DNA. Patient outcomes were analyzed using Kaplan-Meier estimation and a series of 2-factor Cox regression multivariable analyses. ResultsWe identified ESR1 resistance mutations in 30 tumors (0.9%), of which 29 were ER positive (1.1%). In ET-treated disease, presence of ESR1 mutation was associated with poor relapse-free survival and overall survival (2-sided log-rank test P < .001 and P = .008, respectively), with hazard ratios of 3.00 (95% confidence interval = 1.56 to 5.88) and 2.51 (95% confidence interval = 1.24 to 5.07), respectively, which remained statistically significant when adjusted for other prognostic factors. ConclusionsThese population-based results indicate that ESR1 mutations at diagnosis of primary breast cancer occur in about 1% of women and identify for the first time in the adjuvant setting that such preexisting mutations are associated to eventual resistance to standard hormone therapy. If replicated, tumor ESR1 screening should be considered in ER-positive primary breast cancer, and for patients with mutated disease, ER degraders such as fulvestrant or other therapeutic options may be considered as more appropriate.

Associated Factors and Survival Outcomes for Breast Conserving Surgery versus Mastectomy among New Zealand Women with Early-Stage Breast Cancer.

This study aimed to investigate type of loco-regional treatment received, associated treatment factors and mortality outcomes in New Zealand women with early-stage breast cancer who were eligible for breast conserving surgery (BCS). This is a retrospective analysis of prospectively collected data from the Auckland and Waikato Breast Cancer Registers and involves 6972 women who were diagnosed with early-stage primary breast cancer (I-IIIa) between 1 January 2000 and 31 July 2015, were eligible for BCS and had received one of four loco-regional treatments: breast conserving surgery (BCS), BCS followed by radiotherapy (BCS + RT), mastectomy (MTX) or MTX followed by radiotherapy (MTX + RT), as their primary cancer treatment. About 66.1% of women received BCS + RT, 8.4% received BCS only, 21.6% received MTX alone and 3.9% received MTX + RT. Logistic regression analysis was used to identify demographic and clinical factors associated with the receipt of the BCS + RT (standard treatment). Differences in the uptake of BCS + RT were present across patient demographic and clinical factors. BCS + RT was less likely amongst patients who were older (75+ years old), were of Asian ethnicity, resided in impoverished areas or areas within the Auckland region and were treated in a public healthcare facility. Additionally, BCS + RT was less likely among patients diagnosed symptomatically, diagnosed during 2000–2004, had an unknown tumour grade, negative/unknown oestrogen and progesterone receptor status or tumour sizes ≥ 20 mm, ≤50 mm and had nodal involvement. Competing risk regression analysis was undertaken to estimate the breast cancer-specific mortality associated with each of the four loco-regional treatments received. Over a median follow-up of 8.8 years, women who received MTX alone had a higher risk of breast cancer-specific mortality (adjusted hazard ratio: 1.38, 95% confidence interval (CI): 1.05–1.82) compared to women who received BCS + RT. MTX + RT and BCS alone did not have any statistically different risk of mortality when compared to BCS + RT. Further inquiry is needed as to any advantages BCS + RT may have over MTX alternatives.

VAB and MRI Following Percutaneous Ultra-Sound Guided Cryoablation for Primary Early-Stage Breast Cancer: A Pilot Study in Japan

Objective: This study aimed to evaluate the feasibility, safety, and cosmetic outcomes of percutaneous cryoablation (PCA) of breast intraductal carcinoma (IDC) lesions, as well as post-cryoablation magnetic resonance imaging (MRI) as a follow-up tool for detection of residual malignancies and local recurrences. Methods: Eight female patients underwent percutaneous ultrasound-guided cryoablation of breast IDC tumors under local anesthesia without subsequent resection. All patients received radiation- and endocrine therapies (RT, ET). The patients were followed using vacuum-assisted biopsy (VAB), mammography (MG), magnetic resonance imaging (MRI), and Moire Topography for cosmetic outcomes. VAB was performed 6 months following cryoablation treatment for cases 1 and 2 (after starting radiation- and endocrine-therapies) or one month after PCA (cases 3, 4, 5, 6 and 7), prior to RT and ET. One patient declined VAB. Results: Mean age of the patients was 61.9 years, SD 7.7, ages range 53 - 72 years. Mean tumor size was 10.3 mm, SD 2.74, ranged 6.8 - 14.5 mm, median follow-up time was 28 months (range 13 - 34 months). No residual or recurrent malignancies were detected. One minor adverse event was observed: A skin redness in the ablated area; MRI at one-month post-cryotherapy showed various degrees of thermal burns in all patients in the pectoralis major muscle, which were not symptomatic and were resolved by 6 months following PCA. Decrease of fat necrosis areas in the vicinity of ablated ex-tumor was traced with MRI (mean size 54.9 mm, mean decrease after 2 years was 58%) and validated with VAB. Conclusions: Percutaneous cryoablation of early-stage low-risk breast cancer tumors smaller than 15 mm potentially presents a potential substitute for lumpectomy, offering encouraging short- to mid-term oncology results with good cosmesis outcomes. Patients would be able to benefit from local anesthesia in an outpatient setting and a shorter recovery period.

Abstract CT074: Pre-existing ESR1 mutations in early-stage primary breast cancer predict failure of endocrine therapy and poor survival

Abstract Background: More than three-quarters of primary breast cancers are positive for estrogen receptor alpha (ER; encoded by the gene ESR1), the most important factor for directing anti-estrogenic endocrine therapy. Although mutation in ESR1 is known as an acquired mechanism of resistance to endocrine therapy (ET), found in 12-55% of metastatic breast cancers treated previously with ET, the impact of ESR1 mutation on therapy response in primary breast cancer is unclear. Patients and methods: In this study we analyzed 3217 real-world and population-based early-stage primary breast cancers (within the SCAN-B study, ClinicalTrials.gov NCT02306096). Tissues were sampled from initial diagnosis prior to any treatment and analyzed for the presence of ESR1 mutations using RNA sequencing. Mutations were verified by SAGAsafe droplet digital PCR. Results: We identified ESR1 resistance mutations in 30 cases (0.9%), of which 29 were ER-positive (1.1%). In ER-positive disease, presence of ESR1 mutation was significantly associated to poor relapse-free survival (RFS) and overall survival (OS) (p=0.011 and p=0.019, respectively), and moreover predicted poor RFS and OS within the patient group that received ET (p=0.007 and p=0.010, respectively). Conclusions: These results indicate that ESR1 mutations at diagnosis of untreated primary breast cancer are rare, however we confirm for the first time that such early mutations predict eventual resistance to standard hormone therapy in the adjuvant setting. If replicated, tumor ESR1 screening may be considered in ER-positive primary breast cancer and, in mutated cases, ER-degraders such as fulvestrant or other therapeutic options may be considered as more appropriate. Citation Format: Malin Dahlgren, Anthony M. George, Christian Brueffer, Sergii Gladchuk, Yilun Chen, Johan Vallon-Christersson, Cecilia Hegardt, Jari Häkkinen, Lisa Rydén, Martin Malmberg, Christer Larsson, Sofia K. Gruvberger-Saal, Anna Ehinger, Niklas Loman, Åke Borg, Lao H. Saal. Pre-existing ESR1 mutations in early-stage primary breast cancer predict failure of endocrine therapy and poor survival [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT074.

Advantages of intraoperative implant for interstitial brachytherapy for accelerated partial breast irradiation either frail patients with early-stage disease or in locally recurrent breast cancer.

PurposeTo describe the intraoperative multicatheter implantation technique for accelerated partial breast irradiation (APBI) delivered with high-dose-rate brachytherapy (HDR-BT). Secondarily, to evaluate outcomes and toxicity in a series of 83 patients treated with this technique at our institution.Material and methodsRetrospective analysis of a series of patients treated with HDR-BT APBI after intraoperative multicatheter interstitial implant between November 2006 and June 2017 at our institution. We assessed cosmesis, toxicity, overall survival (OS), and disease-free survival (DFS).ResultsEighty-three patients were included: 59 patients (71.1%) with primary early-stage breast cancer and 24 (28.9%) with locally recurrent breast cancer. Tumorectomy was performed in all cases, with intraoperative tumor margin assessment and sentinel node biopsy. Median age was 82 years (range, 44-92). The total prescribed dose was 32 Gy (8 treatment fractions) in 60 patients (72.3%), and 34 Gy (10 fractions) in 23 patients (27.7%). Median follow-up was 40 months (range, 1-136 months). Three-year OS and DFS in the recurrent and primary cancer groups were 87% vs. 89%, and 96 % vs. 97.8%, respectively. Five patients died from non-cancer related causes. No local relapses were observed. Rates of acute and late toxicity were low in both groups. The cosmesis was good or excellent in most of patients treated for primary disease; in patients who underwent salvage brachytherapy for local recurrence, cosmesis was good in 49 patients and fair in 6.ConclusionsThis technique, although time-consuming, achieves good local disease control with a satisfactory toxicity profile in both early-stage and local recurrent breast cancer patients. It may be especially suitable for frail patients.

Survival After Early-Stage Breast Cancer of Women Previously Treated for Depression: A Nationwide Danish Cohort Study.

Purpose The aim of this nationwide, register-based cohort study was to determine whether women treated for depression before primary early-stage breast cancer are at increased risk for receiving treatment that is not in accordance with national guidelines and for poorer survival. Material and Methods We identified 45,325 women with early breast cancer diagnosed in Denmark from 1998 to 2011. Of these, 744 women (2%) had had a previous hospital contact (as an inpatient or outpatient) for depression and another 6,068 (13%) had been treated with antidepressants. Associations between previous treatment of depression and risk of receiving nonguideline treatment of breast cancer were assessed in multivariable logistic regression analyses. We compared the overall survival, breast cancer-specific survival, and risk of death by suicide of women who were and were not treated for depression before breast cancer in multivariable Cox regression analyses. Results Tumor stage did not indicate a delay in diagnosis of breast cancer in women previously treated for depression; however, those given antidepressants before breast cancer had a significantly increased risk of receiving nonguideline treatment (odds ratio, 1.14; 95% CI, 1.03 to 1.27) and significantly worse overall survival (hazard ratio, 1.21; 95% CI, 1.14 to 1.28) and breast cancer-specific survival (hazard ratio, 1.11; 95% CI, 1.03 to 1.20). Increased but nonsignificant estimated risks were also found for women with previous hospital contacts for depression. In subgroup analyses, the association of depression with poor survival was particularly strong among women who did not receive the indicated adjuvant systemic therapy. Conclusion Women previously treated for depression constitute a large subgroup of patients with breast cancer who are at risk for receiving nonguideline breast cancer treatment, which probably contributes to poorer overall and breast cancer-specific survival.

Abstract P3-13-03: Multicenter clinical trial of percutaneous laser ablation for early stage primary breast cancer. Results of 49 cases with radiographic and pathological correlation

Abstract Introduction: Percutaneous laser ablation of early stage primary breast cancer remains investigational. A multicenter, international clinical trial (NCT01478438) was completed to determine feasibility of this technique. Methods: Patients with a single focus of biopsy proven infiltrating ductal carcinoma measuring 20 mm or less by pre-ablation MRI were treated by image-guided percutaneous laser ablation. A laser diode source (805 nominal nanometer wavelength) was used to perform the thermal ablation. Thermal sensors placed at the periphery of the tumor measured achievement of predefined temperature levels, indicating successful ablation. The patients were evaluated by post-ablation mammogram, ultrasound and MRI at 4 weeks post-ablation, after which they underwent surgical excision. Pathology specimens were evaluated by hematoxylin &amp; eosin, CK 8/18, Ki-67 and estrogen receptor staining. Results: Forty-nine of the 61 enrolled patients (ages 42-77, mean age 64 years) undergoing percutaneous laser ablation have finished protocol analysis and are reported in this series. Ablation was considered complete by the treating physician in all cases. The mean tumor size was 11.3 mm. The mean laser time was 15.7 minutes. There were no serious adverse events. Seven patients (14%) reported mild adverse events (pain, blisters, lump). Post-ablation cell viability was determined by MRI and by changes in CK 8/18, Ki67 and estrogen receptor staining. A post-ablation discordance between MRI and pathology was found in evaluation of 4 patients (8%). Three patients (6%) were considered "false negative" with a post-ablation residual tumor burden of less than 2mm which was not detected by MRI. One patient (2%) had a complete pathologic ablation but positive MRI ("false positive"). One patient (2%) had adjacent residual DCIS, visible in retrospect on the pre-ablation MRI and was considered a screening failure. Eight patients (16%) were found to have residual invasive cancer by both post-ablation MRI and pathologic analysis. Complete ablation was confirmed in 36 patients (73%) when evaluated by both post-ablation MRI and pathologic analysis. Conclusion: Percutaneous laser ablation holds promise as an alternative to lumpectomy in the treatment of early stage breast cancer. There is a strong correlation (92%) between findings on post-ablation MRI and changes in CK 8/18, Ki67 and estrogen receptor staining in this series. Additional trials are necessary to determine the long-term curative potential of this technique. Citation Format: Schwartzberg BS, Abdelatif OMA, Lewin JM, Bernard JM, Brehm JL, Bu-Ali HM, Cawthorn SJ, Chen-Seeto M, Feldman SM, Govindarajulu S, Jones LI, Juette A, Kavia S, Maganini RO, Pain SJ, Shere MH, Shriver CD, Smith SG, Valencia A, Whitacre EB, Whitney R. Multicenter clinical trial of percutaneous laser ablation for early stage primary breast cancer. Results of 49 cases with radiographic and pathological correlation. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-13-03.

Monitoring serum HER2 levels in breast cancer patients.

BackgroundWe have developed a new approach to reduce the serum interference for ELISA. The purpose of this study is to investigate if we can use the optimized ELISA (MBB-ELISA) to detect serum soluble HER2/neu (sHER2) in early stage primary breast cancer and monitor its change during treatments.FindingsWe collected sera preoperatively from 118 primary breast cancer patients. Serum samples were also collected sequentially from a subset of patients during and after adjuvant treatment. sHER2 in these samples was measured by the MBB-ELISA. Only 16.7 % of tissue HER2 (tHER2) positive patients had significantly elevated sHER2 levels in serum. Interestingly, sera of some patients with tHER2 negative tumors, including those that were 2+ by IHC but negative by FISH, demonstrated slightly elevated sHER2 levels. Multivariate analysis demonstrated that patients with elevated sHER2 (> = 7 ng/ml) had significantly worse disease free survival. During treatments, sHER2 levels consistently fell in response to adjuvant therapies. Nevertheless, in all 4 patients who developed metastases, a steady rise in sHER2 levels was noted before metastatic disease became clinically evident.ConclusionsFor early stage breast cancers, sHER2 is a poor biomarker to predict tHER2 status, but may have value to supplement tissue tests to identify patients with HER2 tumors. Our results also suggest that sHER2 is worth further study as a biomarker to monitor breast cancer patients during treatments.

Abstract P5-09-01: Nottingham prognostic index plus (NPI+): Validation of the modern clinical decision making tool in breast cancer

Abstract Introduction Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. The Nottingham Prognostic Index Plus (NPI+) is based on the assessment of biological class combined with established clinicopathologic prognostic variables providing improved patient outcome stratification superior to the traditional NPI*. This study aimed to validate the NPI+ in an independent series of BC. Methods A Validation series of 469 primary early-stage BC cases treated in Edinburgh, UK were matched for size, stage and grade to cases from Nottingham, UK used to develop the NPI+ (Training series). Adjuvant therapy was similar in both series except that 143 Edinburgh cases received endocrine therapy whilst the matched Nottingham cases had no adjuvant therapy. However, there was no significant difference in 10 year BC specific survival (BCSS) between the Training and Validation series. Cases, prepared as TMAs, were immunohistochemically assessed for Cytokeratin (Ck)5/6, Ck18, EGFR, Estrogen Receptor (ER), Progesterone Receptor (PgR), HER2, HER3, HER4, Mucin 1 and p53 expression. NPI+ biological class based on the expression of the 10 biomarkers was determined. Subsequent NPI+ prognostic scores were assigned using individual algorithms for each biological class developed using the Training series incorporating clinicopathologic parameters: positive nodes (including nodal stage), tumour size, tumour grade (including mitotic index) and PgR. NPI+ biological classes, prognostic scores and prognostic groups were compared between the Validation and Training series and their role in prediction of patient outcome. A p-value of &amp;lt;0.01 was considered significant. Results As anticipated, there was a comparable distribution of NPI+ biological classes between Training and Validation series: Luminal A, n=143 (31%) vs n=115 (25%); Luminal N, n=99 (21%) vs n=89 (19%); Luminal B, n=75 (16%) vs n=85 (18%); Basal p53 altered, n=54 (12%) vs n=72 (15%); Basal p53 normal, n=37 (8%) vs n=53 (11%); HER2+/ER+, n=31 (7%) vs 18 (4%); HER2+/ER-, n=30 (6%) vs n=37 (8%; X2=13.792, p=0.032). BCSS was analogous between the Validation and Training series in each of the NPI+ biological classes except Luminal B (p=0.042). Similar BCSS was observed in the NPI+ Biological classes of the Training versus Validation series when taking into consideration adjuvant treatment modalities. The mean NPI+ score was similar between the Validation and Training series (2.30 vs 1.89, Pearson’s Regression p=0.079). The NPI+ prognostic groups significantly predicted patient outcome in each molecular class (BCSS, p&amp;lt;0.0001) in the Validation series irrespective of adjuvant treatment. Comparing the BCSS in each of the NPI+ prognostic groups demonstrated there were no significant differences between patient outcome in each of the NPI+ prognostic groups between the Validation and Training series. Conclusion This study validates the NPI+ in an independent series of primary BC confirming its’ reproducibility. The NPI+ provides improved individualised clinical decision making for breast cancer for both prediction of clinical outcome and relevant therapeutic options. Acknowledgements Funded by the MRC References *Rakha EA et al Br J Cancer. 2014 110:1688-97. Citation Format: Andrew R Green, Daniel Soria, Jacqueline Stephen, Desmond G Powe, Christopher C Nolan, Ian Kunkler, Jeremy Thomas, Gill Kerr, Wilma Jack, David Camreron, Tammy Piper, Graham R Ball, Jonathan M Garibaldi, Emad A Rakha, John MS Bartlett, Ian O Ellis. Nottingham prognostic index plus (NPI+): Validation of the modern clinical decision making tool in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-09-01.

Reduction mammoplasty in conservative breast surgery in the early stage of breast cancer

ObjectiveThe aim of this study is to evaluate the application and clinical outcomes (oncological and cosmetic) following oncoplastic conservative surgery using bilateral reduction mammoplasty in conjunction with breast conservation therapy for esthetic purposes.BackgroundBreast cancer is the most common malignancy in women worldwide. Until recently, breast surgery could provide only two options for early-stage breast cancer: either modified radical mastectomy or segmental excision, followed by radiation, but the latter causes breast deformities. Reduction mammoplasty is used as a conservative breast surgery with excision of a large volume of tissue without compromising the cosmetic outcome.Patients and methodsWe studied 17 patients with breast cancer, aged 30-65 years (mean 48.4 years). Patients had been operated on by the reduction mammoplasty technique at Menoufia University Hospital in 2012 and later. Patients were followed up at regular intervals 2 years or more after the operation had been carried out.ResultsReduction mammoplasty is a good technique for conservative breast cancer surgery at its early stage, with fewer complications and better cosmetic results. All specimens showed free resection margins with an average size of 2.4 cm. No recurrence was detected. Postoperative complications were encountered in seven patients in the form of wound infection, seroma, partial skin slough, and asymmetry. Long-term follow-up results are awaited to support the more widespread use of this surgical technique in the definitive treatment of early-stage breast cancer.ConclusionOncoplastic breast surgery is now being used widely as a better substitute for the management of early-stage primary breast cancer with proved safety and efficacy.

HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer

Human epidermal growth factor receptor 2 (HER2) plays an important role in breast cancer progression and provides predictive information for response to targeted therapy including trastuzumab although this is limited. Downstream pathways, such as PI3K/Akt, are associated with HER2/HER3 heterodimerization promoting survival and proliferation amongst cancer cells. Thus, patient outcome and trastuzumab therapy effectiveness might be further characterised by HER2/HER3 dimerisation and its signalling pathways. HER2/HER3 dimerisation status was assessed, using chromogenic in situ Proximity Ligation Assay, in two breast cancer series: early stage primary breast cancer, including 224 HER2+ patients that were not submitted to trastuzumab, and HER2+ breast cancer where patients were treated with adjuvant trastuzumab (n = 143). Levels of biomarkers including PI3K, pAKT, ER, PgR, HER3, BCL2, p53, PTEN and p21 were measured using immunohistochemistry. Levels of HER2/HER3 heterodimers were compared with biomarker expression and patient outcome. An association between high levels of HER2/HER3 dimerisation and absence of hormone receptors, ER and PgR, was observed. We further show for the first time the presence of HER2/HER3 heterodimers and the loss of p21 expression in HER2+ breast cancer predicts a significantly poorer outcome when submitted to adjuvant trastuzumab. Breast cancer patients that reveal high levels of HER2/HER3 dimerisation and loss of p21 are associated with poor survival prognosis in patients with HER2+ breast cancer treated with adjuvant trastuzumab. Further quantification analysis of HER dimer/ligand complexes and downstream signalling pathways will begin to unravel the complex associations with patient outcome and its relationship with sensitivity to targeted treatment.

Upper Limb Physical Function and Adverse Effects After Breast Cancer Surgery: A Prospective 2.5-Year Follow-Up Study and Preoperative Measures

ObjectiveTo examine upper limb physical function and adverse effects after axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) in patients with breast cancer to identify impairments that can inform rehabilitation strategies. DesignProspective longitudinal cohort. Upper limb measurements were studied preoperatively and 2.5 years after breast cancer treatment. SettingHospital setting. ParticipantsTwo groups of patients with early-stage primary breast cancer (N=391): the ALND surgery group (mean age, 55±10y) and the SLNB group (mean age, 57±10y). InterventionsNot applicable. Main Outcome MeasuresArm lymphedema (≥10% increased arm volume relative to control arm volume), grip strength (in kilograms), shoulder mobility, pain intensity during isometric shoulder abduction (on a 100-mm visual analog scale), and body mass index (kg/m2). Parametric/nonparametric tests were used for hypothesized changes and differences, and regression analysis was used for confounding factors. ResultsWe observed more adverse effects in women treated with ALND than with SLNB after 2.5 years (P<.05): arm lymphedema (17% vs 3%), grip strength reduction (12% vs 2%), and shoulder abduction-provoked pain (increase of 6% vs decrease of 50%). The adverse effects were similar for affected and control upper limbs for all outcomes except arm lymphedema, which occurred only on the affected side. ConclusionsAdverse effects in both affected and control/unaffected upper limb were observed after 2.5-year follow-up in both ALND and SLNB groups, but a higher prevalence was observed in the ALND group. Thus, women going through ALND surgery may benefit from further postoperative physical therapy, including resistance and strength exercise, focusing on pain management.