bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic factors and survival of patients with brain metastasis (BM) from breast cancer (BC) who underwent craniotomy.
Authors: Leone Jose Pablo , Cunningham Diana E. , Lee Adrian , Bhargava Rohit , Hamilton Ronald L. , Wiener Erik , Okada Hideho , Brufsky Adam
Published: February 2017

143

Background: BC is the second most frequent cause of BM after lung cancer, with metastases occurring in 10% - 16% of all patients. BM in patients with BC is a catastrophic event that results in poor prognosis. Identification of prognostic factors associated with breast cancer brain metastases (BCBM) could help to identify patients at risk. The aim of this study was to assess clinical characteristics, prognostic factors and survival of patients with BCBM who had craniotomy and resection in a series of patients treated with modern multimodality therapy. Methods: We analyzed 42 patients with BCBM who underwent resection. Patients were diagnosed with BC between April 1994 and May 2010. Cox proportional hazards regression was selected to describe factors associated with time to BM, survival from the date of first recurrence, and overall survival (OS). Results: Median age was 51 years (range 24-74). Median follow-up was 4.2 years (range 0.6-18.5). The mean time to BM from primary diagnosis was 49 months (range 0-206.22). Patients had a median of 2 BM with a median size of 3.25 cm. The proportion of the biological subtypes of BC was ER+/HER2- 25%, ER+/HER2+ 15%, ER-/HER2+ 30% and ER-/HER2- 30%. Brain radiotherapy was given to 28 patients, of which 10 had stereotactic radiosurgery, 7 whole brain radiation, and 11 both. Median OS from the date of primary diagnosis was 5.74 years. Median survival after diagnosis of BM was 1.33 years. In multivariate Cox regression analyses, stage was the only factor associated with shorter time to the development of BM (P=0.059), whereas age was the only factor associated with survival from the date of recurrence (P=0.027) and with OS (P=0.037). Controlling for age and stage, neither the biological subtype of cancer, the radiation modality nor the site of first recurrence showed any impact on survival. Conclusions: Stage at primary diagnosis correlated with shorter time to the development of BM, while age at diagnosis was associated with shorter survival in BCBM. None of the other clinical factors had influence on survival.
Updated results of neoadjuvant chemotherapy with carboplatin AUC 6 and docetaxel 75 mg/m2 in triple-negative breast cancer (TNBC).
Authors: Kern Peter , Kolberg Hans C. , Kalisch Anne , Kimmig Rainer , Pott Dirk , Otterbach Friedrich , Kurbacher Christian M.
Published: February 2017

149

Background: Triple-negative breast cancer (TNBC) is associated with a poor prognosis unless a pathological complete response (pCR) is achieved or almost achieved (near-pCR). Treatment of TNBC remains a challenge as some patients fail to respond to the use of standard anthracyclin-based chemotherapy regimens. Phenotypic and molecular similarities between TNBC and BRCA1-associated breast cancer suggest that TNBC may share the same sensitivity to platinum analogues as tumors associated with BRCA1. Methods: 30 patients with primary, unilateral, non-metastasized TNBC (majority of them cT1 or cT2, two cT4) had to be unsuitable for standard anthracycline-based chemotherapy. They received 6 cycles, respectively in two case sonly 5 cycles, of carboplatin AUC 6 and docetaxel 75 mg/m² q3w. Adverse effects were recorded according to CTCAE V4.07. Primary endpoint was pathological complete response (pCR) and near-pCR, secondary endpoint toxicity. Results: 70% (21/30) of patients had either a pathological complete response (55%; 15/27) or a near-complete response (20%; 6/30) - defined as pT1mic and ypT1a - both being associated with a good prognosis. Eight remaining patients had still good partial response, leaving only low residual cancer burden, which was specified as ypT1, in contrast only one ypT4 tumor. Treatment was well tolerated - grade IV toxicities were predominantly hematological side effects (especially concerning neutropenia) and in 2 cases grade IV edema and joint pain. Carboplatin dose reduction (to an AUC of 5) was required in 5 cases (because of limited renal function, hematological side effects or patient’s age). Conclusions: Our results demonstrate a high-anti-tumour activity of docetaxel 75mg/m² in combination with carboplatin AUC 6, promising high rates of tumour regression and pathological complete remission. The omission of exposure to anthracyclines in patients with considerable heart disease risks seems to be feasible with a good pCR-rate, the latter being a surrogate-marker for long-term survival. Survival data of this trial are currently being updated and will be presented on the Breast Cancer Symposium.
Population-attributable risks for modifiable lifestyle factors and breast cancer in New Zealand women.
Authors: Hayes James
Published: February 2017

15

Background: Breast cancer is an important cause of illness and death in New Zealand women. It is the most commonly registered cancer in women, and the second most common cause of cancer death in women. In 2009, 2,759 women were diagnosed with breast cancer and 658 women died from breast cancer. The incidence of breast cancer is projected to stabilise in New Zealand, but the actual number of women diagnosed with breast cancer will increase because of the increasing proportion of older people and increasing size of the population. Methods: Estimates of the magnitude of modifiable lifestyle risk factors for breast cancer (relative risks and odds ratios obtained from published epidemiological studies) and the prevalence of exposure in New Zealand were used to calculate the population attributable risk percent (PAR%) for each risk factor. The PAR%s show the relative importance of these risk factors, and give an indication of the potential impact of reducing the prevalence of these lifestyle risk factors on the incidence of breast cancer in New Zealand. Results: Six modifiable lifestyle factors were identified for breast cancer. These were obesity, lack of physical activity, high alcohol intake, oral contraceptive use, hormone replacement therapy (HRT), and delayed first birth. The PAR%s for these risk factors ranged from 1% for delayed first birth to 10% for obesity (16% for Maori women and 17% for Pacific women). Conclusions: The most important primary preventive strategies to reduce the risk of breast cancer in New Zealand are promoting lifestyle changes to reduce obesity, promoting regular physical activity (which may in turn reduce the prevalence of obesity), reducing HRT use, and avoiding high alcohol intake. A strategy to promote regular physical activity and reduce obesity could also have other benefits, such as reduced risks of cardiovascular disease and diabetes.
Invasive micropapillary breast cancer: Single-institution experience in the modern era.
Authors: Voci Amy E. , Boafo Camilla , Eaton Anne , Stempel Michelle , Reis- Filho Jorge , King Tari A.
Published: February 2017

150

Background: Invasive micropapillary breast cancer (IMPC) is a rare special histologic type of breast cancer with a propensity for nodal metastases. Molecularly, IMPCs have been classified as luminal B; however, clinical outcome data in the era of targeted therapy are limited. Here we report our institutional experience with IMPC. Methods: We retrospectively reviewed our prospective database from 1995-2009 to identify patients who had surgery for IMPC. Clinical characteristics and outcomes were abstracted from the medical record. Overall survival (OS) was estimated using Kaplan-Meier methods. Factors associated with OS and trends over time were assessed using the log-rank test and Cox regression. Results: We identified 258 patients with IMPC. Median patient age 56yrs (range 26-91), 157(61%) postmenopausal, 147(57%) presented with a palpable mass. The majority of IMPCs were grade 3 (83%), estrogen receptor (ER)-positive (86%) and HER2-neg (81%) with LVI (60%) and nodal metastasis (62%). 194 (75%) patients received chemotherapy (CTX), 204 (81%) hormonal therapy and 37/48 (77%) HER2-pos patients received trastuzumab. At a median follow-up of 55 months (range 1-173mos), 5yr OS is 89.5% with a trend towards improved survival in later yrs; 5 year OS 1995-2005 vs 2006-2009, 85% vs 91%, respectively (p=0.06) Clinical factors associated with OS are shown (Table). Among ER-pos/HER2-neg patients, progesterone receptor (PR) status was strongly associated with 5yr OS. Conclusions: In this large cohort of patients with IMPC treated at a single center, OS was associated with tumor size, PR status, use of CTX and trastuzumab but not with ER or hormonal therapy. These clinical data support the molecular classification of IMPC as luminal B cancers which have a more aggressive clinical behavior than other ER+ cancers. The trend towards improved survival in later years likely reflects the benefits of targeted therapy. [Table: see text]
Phase Ib study of eribulin (ERB) and cyclophosphamide (CTX) in metastatic breast cancer (MBC).
Authors: Truong Thach-Giao , Pelayo Michael , Grabowsky Jennifer A. , Melisko Michelle E. , Magbanua Mark Jesus Mendoza , Moasser Mark M. , Reinert Anne , Hwang Jimmy , Park John W. , Munster Pamela N. , Rugo Hope S.
Published: February 2017

153

Background: ERB is a non-taxane microtubule inhibitor approved for the treatment (Tx) of taxane (TAX) and anthracycline-treated MBC based on improved OS compared to treatment of physician choice. In the adjuvant setting, docetaxel/CTX (TC) was superior to doxorubicin/CTX for DFS and OS. ERB is active in TAX-resistant disease with a low rate of peripheral neuropathy (PN); its primary dose-limiting toxicity (DLT) is bone marrow suppression. We hypothesized that the combination of ERB and CTX would be well tolerated and active in patients with TAX-resistant disease, with potential applicability to the adjuvant setting. Methods: We designed a 3+3 phase Ib study of ERB, administered in 2 escalating doses on day 1 and 8, with CTX 600 mg/m2day 1 every 21 days. Eligibility included PN ≤ grade 1. Correlative studies to identify predictors of response and toxicity included whole blood for SNPs, GWAS, circulating tumor cells (CTC), and archived tumor RNA/protein expression analysis. Toxicity assessment included QoL and evaluation of PN. Results: 6 patients (pts) with MBC, median age 50 (47-63), were enrolled. All pts had prior TAX exposure and 4 pts had baseline grade 1 PN. Tumor characteristics included hormone receptor + (5 pts), HER2+ (2 pts), and triple-negative (1 pt). Median number of prior Tx for MBC was 5 (1-8). No DLTs were observed; the RP2D is eribulin 1.4 mg/m2 on D1 and D8 with CTX D1 600mg/m2. Neutropenia was the only G3/G4 non-DLT observed at this dose, requiring GCSF support in cycle 1 in 2 of 3 pts. All grade toxicities included neutropenia (50%), thrombocytopenia, fatigue, nausea, PN, rash, mucositis, alopecia (33% each), and elevated liver enzymes (17%). Pts received a median of 5.5 cycles (range 3-13), with 3 pts still on Tx. Responses included 2PRs (33%) and 4 SD (67%). 2 pts stopped study Tx for QoL and continued ERB alone. Only 2 pts met threshold of >5CTC/7.5ml at baseline; these had a mean decrease of 90.5% at the start of cycle 2. Conclusions: ERB and CTX is a well-tolerated regimen with promising activity in MBC, with the primary toxicity being neutropenia requiring growth factor support. A phase II study in MBC is underway. Additional correlative studies are ongoing, including molecular analyses of CTC. Clinical trial information: NCT01554371.
Current patterns and costs associated with oral and injectable therapy for metastatic breast cancer in U.S. women: A SEER-Medicare analysis.
Authors: Rugo Hope S. , Clements Karen , McGarry Lisa , Faria Claudio , Teitelbaum April H.
Published: February 2017

156

Background: A prior SEER-Medicare analysis (2001-2008 data) of injectable treatment (tx) after MBC diagnosis (dx) found fulvestrant was the most common 1st-line received (15% of patients) and vinorelbine the most common 2nd- and 3rd-line tx (17% and 13%, respectively). Lifetime cost of treating MBC averaged $110,000. The current study updates this analysis and focuses on a subgroup with prescription drug (Part D) Medicare coverage to evaluate tx patterns and costs including oral agents. Methods: Sample included women with breast cancer dx 2001-2007 with concurrent or subsequent MBC dx, Medicare enrollment from 12 mo prior to dx through 2009 or death, and indication of pharmacologic MBC tx. Subgroup with part D coverage and MBC diagnosis in 2007 was identified. Lines of tx were designated as: 1st-line if 1st agent (or combination if on same day) after dx of MBC; new agents administered > 42 days after the previous agent are a new line, as well as an agent administered > 60 days after last dose of the same agent. Costs were adjusted for length of follow-up. Results: Tx patterns in the overall sample were similar to prior results. Fulvestrant remained the most common 1st-line tx (19% of patients), and vinorelbine the most common 2nd- (18%) and 3rd-line tx (16%). Total costs ($127,000) were higher than in prior study. In the subgroup with Part D coverage (Table) use of oral agents was common for all tx lines. Mean lifetime treatment costs were lower than in overall sample ($102,000) and varied by treatment received. Conclusions: In this population, oral agents are common MBC tx. Inclusion of Part D claims provides a more complete picture of tx patterns in MBC. [Table: see text]
Effects of dose modification of eribulin mesylate in patients with locally recurrent or metastatic breast cancer.
Authors: Faria Claudio , Li Xuan , Powers Annette , Vahdat Linda T.
Published: February 2017

157

Background: Eribulin mesylate is indicated for patients with metastatic breast cancer after treatment with ≥ 2 prior chemotherapeutic regimens. Recommended dosing is 1.4 mg/m2on specific cycle days with options for dose modification (dose reduction/delay) based on severity and duration of specific toxicities. The goal for therapy is to administer the full studied dose; however, for patients experiencing an adverse event (AE) the impact of dose modification has not yet been explored. The purpose of this study was to determine the effects of dose modification due to AEs on duration of therapy. Methods: Data from patients receiving eribulin in a phase III open label, randomized clinical trial evaluating eribulin vs. ‘Treatment of Physician’s Choice’ (E7389-G000-305) was utilized. Analyses were performed on the population with AEs. Patients were classified into a dose modification cohort for any dose reduction/delay related to an AE, or a dose non-modification cohort for patients who did not receive a dose modification but experienced an AE. Descriptive statistics were calculated and survival analyses were conducted. Results: Overall, 462 patients had an AE that was treatment-related: 204 patients (44.2%) had dose modification (delay only [61.8%], reduction only [17.6%], and both [20.6%]), and 258 (55.8%) did not have dose modification. Average age was 55 years, and most patients were Caucasian (92.4%). Patients with dose modification had a mean of 7.36 (±4.56) chemotherapy cycles and a median of 143 treatment days, while patients without modification had a mean of 5.71 (±3.68) cycles and a median of 105 treatment days (p < 0.001). The median PFS was also longer in the dose modification cohort (130 vs. 92 days based on independent review). However, there were no statistically significant correlation between PFS and dose modification after adjusting for the length of treatment exposure using time-dependent and landmark approaches. Conclusions: Delaying or reducing the dose of eribulin in patients who experience AEs may allow patients to remain on therapy longer. Further prospective studies are warranted to confirm the impact on overall efficacy and safety.
Predictive factors of resistance to trastuzumab as neoadjuvant therapy in women with HER2-positive breast cancer.
Authors: Jinno Hiromitsu , Sato Tomomi , Takahashi Maiko , Hayashida Tetsu , Hirose Shigemichi , Kitagawa Yuko
Published: February 2017

168

Background: Despite clinical usefulness of trastuzumab, intrinsic or acquired resistance to trastuzumab is a common clinical phenomenon. However, the mechanisms of resistance to trastuzumab have not been fully elucidated. The objective of this study was to determine the possible mechanisms of resistance to trastuzumab as neoadjuvant therapy in women with HER2-overexpressing operable breast cancer. Methods: Patients with operable breast cancer received 12 cycles of weekly paclitaxel plus weekly trastuzumab before surgery. All tumors were HER2-positive by immunohistochemistry (IHC) or fluorescence in situ hybridization. Expressions of ER, PgR, Ki67, PTEN, phosphorylated IGF-1R (pIGF-1R) and MUC4 were performed by IHC in core needle biopsy samples at baseline. PIK3CA mutation status was evaluated by sequencing of PIK3CA exons 9 and 20 using PCR amplification and direct sequencing. Results: Thirty-seven patients were enrolled and assessable for clinical and pathologic responses. The pCR rate was 48.6% (18/37). Negative, moderate and strong membranous expression of MUC4 was observed in 3 (8.1%), 18 (48.6%) and 12 (32.4%) patients, respectively. Membranous staining for pIGF1-R was negative in 24 (64.9%) patients. PTEN loss was observed in 33.3% (8/24) of the tumor examined. PIK3CA sequence analysis of the 13 tumors identified 2 mutations in exon 20 and 2 mutations in exon 9, corresponding to a PIK3CA mutation frequency of 30.8%. MUC4 status did not affect the pCR rate. Although membranous pIGF1-R expression did not affect pCR rate in hormone receptor-positive patients (66.7% vs. 50.0%), hormone receptor-positive patients with positive membranous pIGF1-R tended to show higher pCR rate compared with negative pIGF1-R (41.2% vs. 0%). PTEN loss and/or PIK3CA mutation were not significantly associated with pCR rate. Conclusions: These data indicate that aberrant downstream signaling caused by loss of PTEN and/or PIK3CA mutation, alternative signaling from IGF-1R and masking with MUC4 were not important mechanisms of resistance to trastuzumab.
Epidemiologic and survival characteristics of breast cancer (BC) among the U.S. Asian Indian and Pakistani women compared with other U.S. population groups: A SEER database study.
Authors: Raza Shahzad , Hossain Akm Mosharraf , Rahman Rubayat , Freter Carl , Abraham Jame
Published: February 2017

19

Background: The Asian Indian/Pakistani population living in the U.S. (USAIP) is a rapidly growing minority group with persistent cancer disparities. According to SEER (Surveillance, Epidemiology, and End-Result) database, BC is the most frequently diagnosed cancer in USAIP women.The customizing therapeutic and preventive approaches are important to improve health quality across different population therefore, we conducted the largest epidemiological and survival disparities of BC in USAIP women. Methods: SEER has been collecting and reporting data on USAIP as a separate ethnic group since 1988. Using 18 SEER registries from 1988-2009 and SEER*Stat 7.0.9, we performed frequency and survival sessions (Kaplan-Meier adjusted for age) on USAIP women with BC and compared with non-Hispanic White (NHW), Hispanics (H),and African American women (AA) with BC. Cox proportional hazards regression analysis was performed to estimate relative risks (RR) on BC mortality after adjusting confounders using SAS v 9.3. Results: A total of 2,750 BC cases reported in USAIP women in SEER database, accounting (38%) of all cancers compare to NHW (30%), H (31%) and AA (32%). The median age at diagnosis in USAIP is significantly less (54 y, p < 0.001) than other ethnicities. Significantly more USAIP (14%, p < 0.001) were diagnosed at age < 40y vs NHW (5%), H (7%) and AA(10%). Compare to NHW, USAIP were more likely to have stages III or IV (22% vs. 18%, p < 0.01); ER/PR+ (84% vs. 75%, p < 0.001); poorly differentiated histology (47% vs. 35%, p < 0.001). 5 yr overall survival is better in USAIP (97%, p <0.01) vs NHW (87%), H (83%) and AA (75%). RR of death from BC in US AIP was higher with age (> 71y), stage III or IV, high grades, ER/PR negative, divorced/widowed, and diagnosis year (1988-1994). Conclusions:This study identifies unique biological features and disparities of BC in US AIP women compared with other US populations. The difference in survival is intriguing, and could be due to differences in tumor biology, access to care, and other epigenetic factors.This study has potential implications for screening and therapeutic recommendations for BC in the US AIP population.
Does removal of DCIS decrease the incidence of invasive breast cancer?
Authors: Killelea Brigid K. , Christy Carla J. , Horowitz Nina Ruth , Tsangaris Theodore , Dixon Mike , Chagpar Anees B. , Grube Baiba J. , Lannin Donald R.
Published: February 2017

2

Background: SEER data have shown that as the incidence of high grade DCIS increases, high grade invasive cancer decreases; but this is not true for low-grade DCIS. The purpose of this study was first to determine what proportion of DCIS is calcified, and second to explore the relationship between grade, invasiveness, and calcification, in an effort to model the effect of removing mammographically detected DCIS. Methods: A single-institution, retrospective review was performed to identify all patients diagnosed with DCIS or invasive cancer from 2003-2011 who had corresponding mammograms. Results: There were 337 cases of pure DCIS, 309 cases of pure invasive tumor, and 847 cases of invasive tumor with a DCIS component. Grade 3 invasive cancers were much more likely to be associated with DCIS compared to grade 2 or 1 cancers. (83% vs. 70% vs. 54%, p<0.001). Of the 1,184 cases with DCIS or a DCIS component, 601 (51%) were associated with mammographic calcifications. The presence of calcifications was strongly associated with DCIS extent, comedo and micropapillary histology, presence of necrosis, and grade of DCIS (p<0.001 for each). High grade DCIS was almost twice as likely to be calcified compared to low grade. Extrapolation to SEER data suggests that there is a large reservoir of undetected, non-calcified DCIS and this is largely of low grade. Conclusions: These findings may explain why breast screening has reduced the incidence of high-grade invasive cancers, through diagnosing and excising high-grade DCIS, and yet has failed to reduce the incidence of low-grade cancers. [Table: see text]
Prognostic significance of p53 overexpression in luminal HER2-negative type breast cancer.
Authors: Kikuchi Shoichi
Published: February 2017

35

Background: In this study, we evaluated the prognostic significance of p53 overexpression, because it was reported that there was a significant correlation between p53 and resistance to endocrine therapy, and prognosis. Methods: A retrospective analysis was performed using 2,332 primary breast cancer patients who underwent surgery between 2001 and 2010. There were 1,899 cases with luminal subtypes (905 cases: HER2-negative and Ki67 low type; 808 cases: HER2-negative and Ki67 high type; and, 186 cases: HER2-positive type), 155 cases with HER2-enriched subtypes, and 278 cases with triple-negative subtypes. Luminal type was defined as ER-positive cell rates ≥ 1%, regardless of PgR status. The cut-off value of the Ki67 index was 20%. Moreover, tumor size, nodal status and nuclear grade were studied in relation to disease free (DFS) and overall survival (OS) using the Cox proportional hazard model. Results: We found that p53 overexpression was present in 10% of the patients and significantly correlated with larger tumors, younger age, positive nodes, a higher grade, negative ER/PgR, a higher Ki67, and positive HER2. The patients with p53 overexpression had significantly unfavorable prognosis, especially in the patients who only received endocrine therapy. There were 26 cases in the luminal HER2 negative and Ki67 low type group that had p53 overexpression and showed a significantly shorter DFS. In the univariate analysis for DFS, p53, Ki67, tumor size, nuclear grade and nodal status were significant factors in luminal HER2 negative type. In the subsequent multivariate analysis for DFS, the p53 status was one of the most significant factors. Conclusions: The p53 overexpression was a significant prognostic factor in luminal type breast cancer. Therefore, the prognostic evaluation of luminal HER2 negative type breast cancer might be improved using an immunopanel, which includes Ki67 and p53. Moreover, it might isolate the patients who are resistant to endocrine therapy.
Presentation and pathology of breast cancer in patients with HIV.
Authors: Rosenblatt Paula , Singh Sukhwant Nikki , Goicochea Lindsay , Kesmodel Susan , Ioffe Olga B. , Chumsri Saranya , Riedel David
Published: February 2017

39

Background: With the use of highly active antiretroviral therapy, it is postulated the prevalence of breast cancer will increase in the HIV infected population. Few studies have evaluated the presentation and pathological features of breast cancer in this population. Methods: Charts of approximately 5,000 HIV patients seen between 2000-2011 at the University of Maryland were reviewed to identify those diagnosed with breast cancer. Demographics, HIV data, cancer clinical presentation, family history, and pathologic findings were collected. Pathologic findings included receptor status (estrogen [ER], progesterone [PR], and human epidermal growth factor 2 [HER2]), grade, stage, lymphovascular invasion (LVI), multifocality/multicentricity (MF/MC), and presence of carcinoma in-situ. Results: Twenty cases of concomitant HIV and breast cancer were identified. At diagnosis of cancer, the median age, CD4 count, and duration of HIV infection were 48 years, 437 cells/mm3, and 6 years, respectively. 47% had a family history of breast or ovarian cancer. 79% self-palpated a mass. Pathologic findings included 18 invasive ductal carcinoma, 1 invasive lobular carcinoma, and 1 ductal carcinoma in-situ. 70% were ER-positive, 50% were PR-positive, and 47% were HER2-positive. 21% were Grade 1, 21% were Grade 2, and 57% were Grade 3. 21% luminal A (ER/PR+, HER2- and Ki67 ≤14%), 52% luminal B (ER/PR+, HER2+ or Ki67>14% or grade 3), 5% HER2 enriched (ER/PR-, HER2+), and 21% triple-negative/basal (ER/PR-, HER2-). 5% were stage 0, 40% were Stage I, 30% were Stage II, 25% were Stage III, and none were Stage IV. LVI was present in 36%, MF/MC was present in 35%, and carcinoma in-situ was present in 82%. Conclusions: Compared to historical data of non-HIV infected individuals, our population presented at a younger age with a strong family history and a greater number of self-palpated breast masses. HIV-infected patients with breast cancer presented with more HER2 positivity, higher grade, less favorable luminal B subtype, and more MF/MC disease. Despite aggressive pathology, most patients still presented with a relatively early stage. Annual screening mammogram at earlier ages should be considered in HIV-infected patients, particularly in patients with positive family history.
Pre-morbid anthropometric measurement and its impact on outcome in early-stage breast cancer in midwestern Ireland.
Authors: Quintyne Keith Ian , Woulfe Bernie , Gupta Rajnish K.
Published: February 2017

45

Background: Obesity has become a grave public health concern of global proportions, especially in many developed counties. Clinical obesity may be defined as a body mass indeed (BMI) of greater than or equal to 30kg/m2. Within recent times, growing interest has been seen for the relationship between obesity and cancer; with it being identified as a significant risk factor. It has also been appreciated that it is one of the greatest modifiable risk factors for malignancy. Obesity at the time of diagnosis of early-stage breast cancer (EBC) has been associated with poor outcome, especially breast-cancer specific survival. The potential mechanism for this has been linked to several factors including: associated adverse disease features; hormonal influences; co-morbidities that can interfere with therapy; and other yet unknown pathways. We herein report our experience on patients with newly diagnosed EBC and related pre-morbid anthropometric data and its impact on their outcome in an ambulatory Medical Oncology practice in Mid-Western Ireland. Methods: Study period: 01/01/2001 – 31/12/2010. Retrospective data was derived from (1) MWCC Oncology database, (2) pathology reports, and (3) patient files. Data was collated and entered into an Access database and exported into IBM SPSS Statistics 20 version for statistical analysis. Results: One thousand and forty-one (1,041) patients with EBC were identified and analysed. Median age: 55 years (23 – 87 years). Median follow-up: 5.04 years. BMI distribution revealed: Underweight (<18.5kg/m2): 1%; Normal (18.5 – 25kg/m2): 33%; Overweight (25.1 – 30kg/m2): 39%; and Obese (>30kg/m2): 27%. It was noted that obese patients had disproportionately later age of presentation, larger tumours, ductal carcinoma on histology and a smoking history (including current and former smokers). Obese patients accounted for 50% of the non-cancer related deaths observed. Obese patients showed poorer survival in all categories, but it was only statistically significant for non-cancer related deaths. Conclusions: Pre-morbid anthropometric data has shown that obese patients had poorer outcome, and highlights that potential intervention can have impact on improving outcome in EBC.
Predictors of regional recurrences in breast cancer patients with negative sentinel node.
Authors: Matsumoto Akiko , Takahashi Maiko , Hayashida Tetsu , Jinno Hiromitsu , Kitagawa Yuko
Published: February 2017

51

Background: For patients with clinically node-negative, early-stage breast cancer, sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as a standard method for staging of regional lymph nodes. Regional recurrences after negative (SLNB) have generally been reported in the range of 0.5 to 2% and factors associated with regional recurrence in patients with negative SLNB are still to be elucidated. In this study, we evaluated regional recurrence rates and predictors of regional recurrences in patients with negative SLNB. Methods: Between January 2001 and December 2012, 1,322 patients with clinical node-negative invasive breast cancer less than 3cm underwent SLNB at Keio University Hospital. Of 1,322 patients with SLNB, 1,033 patients with negative SLNs were included in this study. Sentinel lymph nodes (SLNs) were detected using a combined method of blue dye and small-sized technetium-99m-labeled tin colloid. Intraoperative frozen examination was performed with hematoxylin and eosin (HE) staining. SLNs, fixed and embedded in paraffin, were additionally diagnosed with HE staining and immunohistochemical analysis. Results: Median age was 57.0 years (range, 25-89) and median tumor size was 1.9cm (range, 0.5-6.0cm). After a median follow-up of 54.8 months, there were 13 regional (1.3%) and 26 distant recurrences (2.5%). Median disease-free interval of regional and distant recurrences was 32.6 and 22.7 months, respectively (p=0.761). Higher nuclear grade (NG) was significantly correlated with regional and distant recurrences (p=0.001 and p=0.008). The rate of lymphovascular invasion (LVI) was significantly higher in patients with regional recurrences comparing with patients without recurrences (58.3% vs. 27.6%, p=0.026), however LVI was not a significant predictor of distant recurrences (p=0.072). Estrogen receptor negativity was significantly correlated with distant recurrences (p=0.013), whereas it was not associated with regional recurrences (p=0.626). Conclusions: Regional recurrences were rare in early-stage breast cancer patients with negative SLNB. LVI and NG can be used as predictive factors of regional recurrences after negative SLNB.
Sentinel node biopsy after neoadjuvant therapy: Relevance of sentinel node micrometastases, isolated tumor cells, and value of immunohistochemistry.
Authors: Boileau Jean-Francois , Poirier Brigitte , Basik Mark , Holloway Claire , Gaboury Louis , Sideris Lucas , Meterissian Sarkis H. , Arnaout Angel , Brackstone Muriel , McCready David R. , Karp Stephen Eric , Wright Frances Catriona , Younan Rami , Provencher Louise , Patocskai Erika , Omeroglu Atilla , Robidoux Andre
Published: February 2017

52

Background: Sentinel node biopsy (SNB) is used in breast cancer patients that present with clinically negative nodes. In this setting, most guidelines do not support the use of immunohistochemistry (IHC) and recommend against completion node dissection (CND) when only isolated tumor cells (pN0(i+)) or micrometasases (pN1mi) are identified. When SNB is used after neoadjuvant therapy (NAT), the relevance of ypN0(i+) and ypN1mi sentinel nodes (SNs) and the value of IHC are not well established. The goals of this study are to determine if CND should be recommended in the presence of ypN0(i+) or ypN1mi SNs and if IHC should be used to evaluate SNs after NAT. Methods: From March 2009 to December 2012, 152 women with biopsy proven node positive breast cancer were accrued to the multicentric prospective SN FNAC trial. After NAT, SNB was followed by a CND in all participants. SNs were cut in serial slices no thicker than 2 mm. Hematoxylin and eosin stains (H and E) were done on all slices, and if negative, IHC was used. The size of the largest SN metastasis and the primary method of identification (H and E or IHC) were recorded. ypN0(i+), ypN1mi and ypN1 SNs were considered as positive. Pathology was centrally reviewed. Results: 145 women were eligible for the trial. Axillary pathologic complete response rate = 34% (49/145). SNB success rate = 88% (127/145). False negative rate = 8.4% (7/83). If ypN0(i+) SNs are classified as node negative, the false negative rate is increased to 13.3% (11/83). For patients with ypN0(i+) (n=7), ypN1mi (n=8) and ypN1 (n=61) SNs, the rates of non-SN involvement are 57%, 38% and 56% respectively (p=NS). 40% (27/68) of positive SNBs are primarily detected by IHC. This is increased to 64% (9/14) for the identification of SN metastases ≤ 2mm. Conclusions: After NAT, particularly when presenting with biopsy proven node positive breast cancer, patients with ypN0(i+) and ypN1mi SNs have a significant rate of non-SN involvement. In the absence of evidence to show that a CND can be safely avoided, efforts should be made to identify even minimal amounts of disease when SNBs are done following NAT. IHC is useful to increase the detection of small SN metastases in this setting. Clinical trial information: NCT00909441.
Association of MRI and locoregional recurrence (LRR) rates in ductal carcinoma in situ (DCIS) patients treated with or without radiation therapy (RT).
Authors: Pilewskie Melissa Louise , Olcese Cristina , Eaton Anne , Patil Sujata , Morris Elizabeth Ann , Morrow Monica , Van Zee Kimberly J.
Published: February 2017

57

Background: Perioperative MRI is frequently obtained in women with breast cancer; however, studies have not shown decreased rates of re-excision, and some report unnecessary increases in mastectomy rates. We examined LRR rates among women with DCIS who underwent perioperative MRI as compared to those who did not. Methods: All women who underwent breast-conserving surgery for DCIS in 1997-2010 were included from a prospectively maintained database. Patient characteristics and rates of LRR were compared in women with and without an MRI. Univariate and multivariate analyses were performed. Analysis was repeated in the subset of women who did not receive RT. Results: 2,321 cases were identified; 596 had MRI and 1,725 did not. Women who had MRI were younger, more likely to be premenopausal, have a family history of breast cancer, have a clinical presentation, receive RT and endocrine therapy, be treated in later years, and had fewer close/positive margins. At median follow-up of 57 months there were 184 IBTRs; 5-year LRR rates were 8.5% (MRI) and 7.2% (no MRI) (p = 0.52), and 8-year rates were 14.6% and 10.2%, respectively. MRI was not associated with lower LRR rates after adjustment for age, menopausal status, family history, presentation, adjuvant therapy, margin status, number of excisions, and year of surgery in both the entire cohort and in the subgroup who did not receive RT. Select factors from multivariate analysis for patients with all covariates available are shown in the Table. Conclusions: We observed no association between perioperative MRI and LRR rates for patients with DCIS, even when RT was not given. The benefit of perioperative MRI for DCIS remains uncertain. [Table: see text]
The impact of recurrence score (RS) performed on pretreatment (Tx) core biopsies (CB) in predicting response to neoadjuvant chemotherapy (NCT) in patients (Pts) with ER+ breast cancer (BC).
Authors: Soran Atilla , McGuire Kandace P. , Ahrendt Gretchen , Bonaventura Marguerite , McAuliffe Priscilla F. , Diego Emilia , Serrano Merida , Johnson Ronald
Published: February 2017

63

Background: The Oncotype DX 21-gene assay is beneficial in predicting disease-free survival and local regional relapse in hormone receptor BC. The ability of the assay to predict response of primary BC to NCT is less well studied. We hypothesize a (+) association exists between the RS result on pre-Tx CB and % tumor response (%TR) after NCT on final pathology. Methods: Pre-Tx RS was measured on paraffin-embedded CB from 60 pts with ER+ Her2(-) BC who then received NCT and for whom post-Tx pathology was available. %TR is calculated as 100 x (pre-Tx size – post-Tx size)/pre-Tx size. Pre-Tx tumor size was determined using imaging measurements selected in the following preferential order: MRI, US or mammogram. Post-Tx tumor size was calculated as the product of: maximum dimension of tumor-bed/fibrosis and % change in cellularity (compared with pre-therapy biopsy). Partial response (PR) is defined as ≥50% reduction in TR. Results: Mean pre-Tx tumor sizewas 4.8 (range 1-23) cm. 83% of pts were clinically lymph node (-). Nottingham Score was >6 in 93%. Breast conserving surgery was performed in 17 (28%) pts. Median RS was 20 (range 3-69). Median %TR was 42 (range 0-97)%. There were no pCRs. PR was observed in 43% of pts. No association was found between %TR and pre-NCT tumor size, age, Nottingham score or node status (p>0.05). No association for the RS as a continuous or categorical variable with %TR (p>0.05) was seen. There is a non-significant (p=0.07) trend toward increased response to NCT with increasing RS. Response to NCT improved as values of ER (p=0.02) and HER2 (p=0.007), by RT-PCR as reported with the RS, decreased. Conclusions: In the subset of patients with ER+ BC, where NCT was recommended to affect tumor downstaging, RS did not successfully discriminate pts that would respond to NCT as measured by %TR. While there was a trend toward better response with higher scores, the result was nonsignificant. The use of this genetic assay to discriminate between NCT and hormonal therapy requires further study. [Table: see text]
Impact of endocrine therapy in early-stage breast cancer on time to locoregional recurrence.
Authors: Menjak Ines B. , Maki Ellen , Berman Hal K. , Chung Caroline , McCready David R. , Sridhar Srikala S.
Published: February 2017

64

Background: Locoregional recurrence (LR) remains a major source of morbidity and mortality in breast cancer. Our primary aim was to evaluate the impact of endocrine therapy (ET) on time to LR. Methods: A retrospective chart review of breast cancer patients (pts) treated with lumpectomy and locoregional radiation from 1999-2005 at the Princess Margaret Cancer Centre was carried out. LR was defined as ipsilateral breast or lymph node recurrence. Kaplan-Meier estimates of survival and univariate analyses were performed for age, menopausal status, tumor and nodal stage, grade, receptor status, adjuvant chemotherapy (AC) and ET. Results: Of 440 pts evaluated, the mean age at primary resection was 56 years (yrs) (range 40-79), and 67% were postmenopausal. The majority had ductal carcinomas (87%) and grade 1-2 (68%) tumors. Tumor distribution was 315 (72%) T1, 120 (27%) T2, 4 (1%) T3; 138 (31%) were node positive. Receptor status was ER/PR+HER2- 206 (47%), ER+PR+HER2unknown 80 (18%), ER-PR-HER2unknown 41 (9%), and triple negative 37 (8%). AC was used in 190 (43%). ET (tamoxifen and/or aromatase inhibitors) was initiated in 294 (84%) eligible pts, and 267/294 (91%) completed a minimum duration of ≥2 yrs. Overall, LR occurred in 24 (5%) pts, and 8/24 (33%) pts with LR also had distant metastases. Average time from surgery to LR was 5.4 yrs (range 8 months-12 yrs). The average duration of ET in pts with LR was 4.3 yrs (range 0-8), and 5.8 yrs (range 0-12) without LR. Of ER/PR+ pts with LR, 3/15 (20%) did not receive ET. At the time of LR, 5 (33%) pts were receiving ET. After stopping ET, 2 (13%) recurred 0-2 yrs, 3 (20%) at 4-5 yrs, and 2 (13%) at 7-8 yrs. Treatment with at least 2 yrs of ET predicted for fewer recurrences: at 2 yrs LR-free rate was 100% vs 90% for <2 yrs ET; at 5 yrs 99.6% vs 84%; and at 8 yrs 98.2% vs 84% (p=0.0092). ER/PR+HER2- pts had lower LR risk (p=0.028), and ER-/PR-/HER+ had higher LR risk (p=0.029). The remaining variables were not associated with risk of LRs. Survival post-LR was 90% (95%CI 64-97%) at 2 yrs and 65% (95%CI 34-84%) at 5 yrs. Conclusions: Pts who completed at least 2 yrs of ET had significantly lower risk of LR. The average time to LR was 5.4 years, and pts with LR had decreased survival at 5 yrs post-recurrence.
Propensity-score matched pair comparison of brachytherapy-based accelerated partial breast irradiation versus whole breast Canadian hypofractionation.
Authors: Chen Peter Y. , Wilkinson John Ben , Shah Chirag , Wobb Jessica , Wallace Michelle , Ye Hong , Marina Ovidiu , Benitez Pamela , Dekhne Nayana , Brabbins Donald S. , Vicini Frank
Published: February 2017

65

Background: Given the initial report of the RAPID trial with greater morbidity for 3-D conformal external beam APBI [3D-APBI] vs. Canadian Hypofractionation [CHfx], a propensity-score matched-pair analysis of brachytherapy-based APBI [B-APBI] vs. CHfx was performed to assess efficacy, toxicities, and cosmesis. Methods: Early-stage breast cancer patients treated with B-APBI or CHfx were reviewed. With ≥ 1y follow-up [FU], B-APBI (n=108) pts were matched 1:1 to CHfx (n=108) by age, T-stage, nodal/ER status, endocrine or chemotherapy and laterality. Ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), distant metastasis (DM), contralateral breast cancer (CLBC), cause-specific survival (CSS), overall survival (OS) and disease-free survival (DFS) were compared by Kaplan-Meier (log-rank test). Toxicities were graded per CTCAE v3 and comesis per Harvard criteria. Results: Median FU was 5.7 y (1.0-17.8) for B-APBI and 2.1 y (1.0-5.7) for CHfx [p < 0.001]. Patients did not differ by match criteria. In comparing B-APBI to CHfx, median age was 69.0 vs. 70.0 [p = 0.72]; for laterality, T-stage, nodal/ER status, endocrine or chemotherapy, no significance [NS] was noted between the 2 groups [p = 0.79, 1.0, 0.60, 0.09, 0.15, and 0.16 respectively]. Comparing B-APBI to CHfx, NS was seen in 5-y actuarial rates of IBTR [1% vs. 0% p = 0.35], RR [0% both], DM [3.4% vs. 0% p = 0.25], CLBC [2.3% vs. 2% p = 0.63], CSS [94.3% vs. 100% p = 0.47], OS [87.7% vs. 88.3% p = 0.71] & DFS [97.5% vs. 100% p = 0.52]. The majority of maximal late toxicities were Gr 1-2. Of toxicities analyzed, including pigmentary changes, edema, pain, induration, volume reduction, telangiectasia, fat necrosis and seroma, only Gr 2-3 hyperpigmentation was significantly higher in the CHfx [8% B-APBI vs. 22% CHfx p = 0.017]. Good/excellent cosmesis was seen in > 93% in both groups. Conclusions: With FU of >5 yrs, B-APBI has similar efficacy and cosmesis but less morbidity vs. CHfx; the lesser toxicity of B-APBI vs. CHfx is in contradistinction to the RAPID results comparing 3D-APBI vs. CHfx. Further FU and more patients are needed to substantiate these findings.
Does anesthesia type influence breast cancer outcomes?
Authors: Tsigonis Abraham , Landercasper Jeffrey , Al-Hamadani Mohammed , Linebarger Jared , Vang Choua , Marchese Edward , Krause Forest , Johnson Jeanne , Marcou Kristen , Hudak Jane
Published: February 2017

66

Background: Surgery maintains a central role in the local treatment of Stage 0-III breast cancer. Recent studies suggest patient immunity is altered by general anesthesia (GA), potentially worsening cancer outcomes. A single retrospective case review has concluded that breast cancer patients receiving regional anesthesia with paravertebral block (PVB) anesthesia had better cancer outcomes compared to patients receiving GA, but these conclusions have not been validated. We hypothesized that local regional anesthesia (LRA) would be associated with better cancer outcomes compared to GA. Methods: We performed a retrospective review of Stage 0-III breast cancer patients undergoing surgery in a single center during a nine year period ending 1/1/2010. Patients undergoing neoadjuvant therapy or major flap reconstruction were excluded. Data regarding patient, tumor and treatment factors known to influence cancer outcomes were collected. Overall survival (OS), disease free survival (DFS), local regional recurrence (LRR), and ipsilateral breast tumor recurrence (IBTR) were calculated by Kaplan-Meier method with Log-Rank comparison. Results: We analyzed 1,107 patients. Median age was 64 years (range 24-97). Median and longest follow-up were 5.5 and 12.5 years. GA was utilized for 461 (42%) patients, and 646 (58%) received LRA. Initial operation was breast conserving in 796 (72%) and mastectomy in 311 (28%). Forty two patients died from breast cancer (crude mortality 3.8%). LRR occurred in 34 patients (3%). LRA was used more than GA in patients with lower grade and stage, smaller tumors, positive hormone receptor status, and negative nodal status (p<0.001). We identified no differences in OS, DFS, LRR or IBTR in comparison of GA to LRA. Conclusions: Type of anesthesia for breast cancer surgery did not affect cancer outcomes in our institution. This result differs from the only prior published clinical report on this topic.