bluuebunny/crossref_metadata_2025 huggingface dataset:
Variations in care for operable breast cancer and outcomes between rural and metropolitan centers in Australia
Authors: Craft P. S. , Buckingham J. , Dahlstrom J. E. , Beckmann K. , Zhang Y. , Stuart-Harris R. , Jacob G. , Roder D. , Tait N.
Published: August 2020

e11517

Background: The causes of variation in breast cancer survival remain uncertain. Care provided to women with breast cancer may vary in relation to both the care setting and characteristics of the clinicians. Methods: To compare the outcomes of management of breast cancer treated in rural and metropolitan centers, a prospective audit of breast cancer in a region of Australia was undertaken. Over a nine-year observation period 2102 women with invasive breast cancer underwent potentially curative surgery. Treatments received, including systemic adjuvant therapy, were compared to contemporary guideline-based indicators. Breast cancer specific mortality was analyzed using Cox proportional hazards models. Results: Overall agreement of received treatment with the indicators was high. Women treated within rural centers were, however, much less likely to receive post operative radiotherapy after breast conserving surgery (86.4% vs. 97.0%; p<0.001). The overall recurrence rate, including distant metastases, for all women was 11.6%. Local or regional recurrence was more frequent in rural centers compared with metropolitan centers (4.1% versus 2.1%; p=0.05). Breast cancer mortality was increased in women with large tumors, high grade disease, and positive axillary lymph nodes. Non-compliance with treatment guidelines was associated with a trend towards increased breast cancer mortality (HR=1.55; p=0.056). After adjustment for these factors and patient age, undergoing surgery in rural centers was associated with increased breast cancer mortality (HR=1.84; p<0.001). Although women treated in rural centers were older, their cancer stage and tumour characteristics were similar to those of women treated in metropolitan centers. Non-cancer related mortality was elevated in women treated in rural centers compared with women travelling to a city for surgery (HR=2.08; p=0.005). Conclusions: Increased non-cancer related mortality in rural treated women suggests increased medical co-morbidity in this group, which may have influenced treatment choices and outcomes. Low rates of adjuvant radiotherapy were noted for women treated in rural centers. In addition, clinically significant differences in outcome, including breast cancer mortality, were observed.

No significant financial relationships to disclose.
Trastuzumab cardiotoxicity: FDA review of four adjuvant breast cancer clinical trials leading to trastuzumab marketing approvals
Authors: Fedenko K. , Cortazar P. , Keegan P. , Pazdur R.
Published: August 2020

e11520

Background: Trastuzumab can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure (CHF), and decreased left ventricular ejection fraction (LVEF). Methods: Data was reviewed from 9837 patients in four randomized trials (NCCTG 9831, NSABP B-31, HERA, and BCIRG-06) that supported trastuzumab HER2 overexpressing adjuvant breast cancer approval. Results: Trastuzumab can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Herceptin can also cause asymptomatic decline in LVEF. There is a 4−6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving trastuzumab as a single agent or in combination therapy compared with those not receiving trastuzumab. The highest absolute incidence occurs when trastuzumab is administered with an anthracycline. Clinical trials NCCTG 9831, NSABP B-31, and BCIRG-06 included arms with doxorubicin- cyclophosphamide (AC) followed by a taxane plus trastuzumab. Among 32 patients receiving adjuvant chemotherapy from studies NCCTG 9831 and NSABP B-31 who developed CHF, one patient died of cardiomyopathy and all other patients were receiving cardiac medication at last follow-up. Approximately half of the patients recovered to a normal LVEF (defined as ≥ 50%) on continuing medical management at the time of last follow-up. In BCIRG-06 the incidence of CHF was six (6) fold higher in the AC followed by docetaxel plus trastuzumab arm as compared to AC followed by docetaxel. There was a lower incidence of CHF in the non-anthracycline TCH (docetaxel, carboplatin and trastuzumab) arm in BCIRG-06 comparable to trastuzumab monotherapy. Conclusions: Cardiotoxicity manifesting as sub-clinical and clinical cardiac failure is a known side effect of trastuzumab. In an era where trastuzumab is given earlier in the treatment of breast cancer (adjuvant setting), the safety of continuation or resumption of trastuzumab in patients with trastuzumab-induced left ventricular cardiac dysfunction has not been studied.

No significant financial relationships to disclose.
Epirubicin (E) followed by cyclophosphamide, methotrexate, 5-fluorouracil (CMF) versus paclitaxel (T) followed by epirubicin and vinorelbine (EV) in patients (pts) with high-risk operable breast cancer
Authors: Boccardo F. , Rubagotti A. , Guglielmini P. , Sismondi P. , Farris A. , Amadori D. , Agostara B. , Gambi A. , Catalano G. , Faedi M.
Published: August 2020

e11521

Background: > 3 N+ pts have a poor outcome, even in the presence of otherwise favourable phenotypic features. CT, alone or combined with endocrine therapy (ET) in hormone receptor (HOR)+ pts, is the gold standard for these women. However questions still exist about the optimal CT regimen. Methods: 244 >3N+ pts were randomized to either four 3-weekly courses of E (100 mg/sqm,d 1)followed by four 4-weekly cycles of CMF (600, 40, 600 mg/sqm, dd 1,8)(E-CMF:N=122)or four 3-weekly courses of T (175 mg/sqm, d1) followed by four 3-weekly cycles of EV (E:75 mg/sqm, da 1; V: 25 mg/sqm dd 1,8;.) (T-EV:N=122). After CT, tamoxifen (plus a LH-RH analog in menstruating women ) was given for 5 years to all HOR+ pts.S was the primary end-point. Results: At 82 mos median f-up, S and RFS did not differ significantly between groups (7-yr S: E-CMF:76%,T- EV:74%;adjust. HR: 0.89;0.54–1.49;p=0.7; 7-yr RFS: E-CMF:67%,T-EV:63%;adjust. HR: 0.95;0.61–1.47;p=0.8;).Cox analysis confirmed no difference between treatments. However RFS forest plots showed some heterogenity in CT effect according to HOR and HER2 status: E- CMF was superior to E-TV in HOR + pts (HR=0.43; CI 0.20–0.93 p=0.03),irrespective of HER2 status, but it was inferior (HR=1.91;CI 0.48- 7.64;p=0.4) in triple negative pts. The two regimens showed different toxicity profiles;however toxicities were manageable and there were no difference in the %of pts receiving all the 8 planned CT cycles (E-CMF: 87.6%;T-EV:81.1% p=0.2) or who discontinued CT (E-CMF: 12.8%; T-EV: 18.9% p=0.2). Conclusions: T-EV was not superior to E-CMF which,combined with ET, still represents an adequate choice for this high risk pts subset, especially for HOR+ pts.

No significant financial relationships to disclose.
Adjuvant breast cancer: FDA approval overview
Authors: Cortazar P. , Johnson J. , Justice R. , Pazdur R.
Published: August 2020

e11529

Background: Improved disease-free survival (DFS) in randomized controlled trials (RCT) is the primary basis for approval of adjuvant breast cancer (ABC) treatments. Methods: Review of clinical trials leading to new drug approvals for ABC. Results: DFS is a composite endpoint defined as the time from randomization to the earliest occurrence of invasive loco-regional recurrence, invasive contralateral breast cancer, DCIS, distant metastases, second primary tumors or death from any cause. Trials supporting marketing approval have used inconsistent DFS definitions that included different components of this endpoint. Basis of paclitaxel approval following AC was superior DFS (HR= 0.78; 95% CI 0.67–0.91, p=0.002) and overall survival (HR=0.74; 95% CI 0.60–0.92, p=0.0065). Trastuzumab approval as part of a treatment regimen was based on 4 clinical trials that showed improved DFS. Docetaxel approval was based on improved DFS of the docetaxel-containing combination regimen TAC compared to FAC (HR: 0.74; 2- sided 95% CI=0.60–0.92, p=0.0047). Doxorubicin approval was based on a meta-analysis of six ABC trials comparing doxorubicin- containing regimens to CMF. Analyses demonstrated that doxorubicin-containing regimens retained at least 75% of the historical CMF adjuvant effect on DFS (HR: 0.91; 95% CI 0.82–1.01) and OS (HR: 0.91; 95% CI 0.81–1.03). Epirubicin approval was based on a longer relapse free survival (RFS) of the epirubicin-containing combination therapy (CEF-120) compared to CMF (HR=0.76; 95% CI 0.60–0.96, p=0.013). Tamoxifen approval was based on an overview of tamoxifen adjuvant therapy. Ten-year survival was 61.4% for tamoxifen vs. 50.5% for control (p < 0.00001) and RFS was 59.7% for tamoxifen vs. 44.5% for control (p < 0.00001). Anastrozole approval was based on a longer DFS (HR: 0.87; 95% CI=0.78–0.97, p=0.0127). Letrozole was based on a superior DFS (HR= 0.62; 95% CI 0.49–0.78, p=0.00003). Exemestane approval was based on improved DFS (HR: 0.65; 95% CI=0.53–0.79, p=0.00001). Conclusions: Although DFS was the basis for approval in most of the ABC clinical trials, the endpoint definition varies between trials. DFS definition should be standardized in ABC clinical trials to permit consistent interpretation and analysis and to facilitate cross-trial comparisons.

No significant financial relationships to disclose.
Early recurrence of breast cancer after sentinel node navigation surgery: A multicenter prospective study in Japan
Authors: Imoto S. , Morita S. , Kitajima M. , Aikou T. , Kitagawa Y.
Published: August 2020

e11530

Background: To assess lymphatic mapping technique and prognosis after sentinel node navigation surgery (SNNS), the Japanese society for SNNS conducted a non-randomized multi-center prospective study on SNNS in early breast cancer. Primary endpoint is to evaluate the success rate and adverse events of SNNS, and secondary endpoint is to observe the outcome of patients who underwent SNNS during 5 years. Methods: We demonstrated the results of primary endpoint at 2007 ASCO annual meeting (#606). Fourteen hundred and sixty-eight cases had pre-registration from 65 investigators at 23 institutions between July 2004 and October 2005. As 46 cases were withdrawn for some reasons and 11 cases were diagnosed as benign disease, 1,411 cases were entered in this study and will be observed until 2010. At this meeting, early recurrence at 3 years follow-up is reported. Results: As of June 2008, 38 of the 1,138 cases (3%) treated with SNNS alone and 16 of the 258 (6%) cases treated with SNNS followed by axillary lymph node dissection (ALND) relapsed. Seven cases died of disease. From the patient background, 50 cases had invasive ductal carcinoma, one had non-invasive ductal carcinoma, and three had special type. Thirty-three cases had negative nodes, 3 had micrometastatic nodes, and 18 had macrometastatic nodes. Fifty-two cases received chemotherapy and/or endocrine therapy. Regional recurrence including axillary, parasternal, and/or supraclavicular nodes was found in 11 cases after SNNS and in 2 cases after SNNS followed by ALND. Conclusions: Annual regional recurrence rate after SNNS was about 0.3%. SNNS in breast cancer is reliable to optimize surgical management in the axilla without increase of regional recurrence.

No significant financial relationships to disclose.
Validation of Adjuvant!Online on Slovenian collective of early breast cancer patients
Authors: Ravnik M. , Sadikov A. , Snoj N. , Nussdorfer P. , Cufer T.
Published: August 2020

e11532

Background: Adjuvant!Online is a very useful tool for prognosis assessment of early breast cancer (EBC) patients. In the validation study, made on mostly untreated (45%) Canadian EBC patients, Adjuvant!Online proved to be a very reliable prognostic tool. The aim of our study was to validate Adjuvant!Online on EBC patients mainly treated with some kind of adjuvant systemic therapy. Methods: 753 EBC patients diagnosed and treated at the Institute of Oncology Ljubljana, Slovenia, with at least 10-year follow-up were included into the study. All patients received radical local therapy. Adjuvant chemotherapy (ChT) was either CMF or anthracycline-based schema and hormonal therapy (HT) was mainly tamoxifen. Adjuvant!Online 8.0 individual prediction of OS was calculated (with default value of “minor problems” as comorbidity for all patients). The average prediction over all patients was compared to the observed 10-year OS. Results: The predicted and observed 10-year OS of the whole group were 65.5% and 61.5%, respectively. The differences between predicted and observed OS did not differ substantially in the subgroups of patients stratified according to the classical prognostic factors, however, a large difference was found when stratifying by adjuvant systemic therapy. The puzzling difference in patients without systemic therapy (ST) can be both due to small group size and due to special selection of these patients (comorbidity). Conclusions: According to our observation, Adjuvant!Online is a reliable tool for prognosis assessment in EBC patients treated with HT, but it seems to overestimate prognosis in patients treated with ChT, alone or in combination with HT. This is evident even for our collective of EBC patients mainly treated with the first generation ChT - CMF or anthracyclines. Apparently, both Adjuvant!Online and Overview overestimate the positive effect of ChT, disregarding the biologic characteristics of the tumors and inherent effect of HT in HR+ patients.

[Table: see text]

No significant financial relationships to disclose.
Serum molecular signatures of weight change during early breast cancer chemotherapy
Authors: Stebbing J. , Keun H. C. , Sidhu J. , Patterson M. , Bloom S. R. , Amber V. , Coombes C. , Marconell H. , Pshezhetskiy D.
Published: August 2020

e11534

Background: Weight gain in women receiving chemotherapy following breast cancer diagnosis has negative implications on quality of life and those who gain weight during treatment appear to be at higher risk of disease recurrence. The mechanism(s) implicated in chemotherapy associated weight gain are poorly understood. Methods: To investigate this further, we assessed the metabolic, cytokine and appetite related peptide alterations before and during adjuvant FEC chemotherapy for early breast cancer in post-menopausal women, and correlated these with body mass measurements. Specifically, we performed global metabolic profiling (metabonomics/ metabolomics) using 1H nuclear magnetic resonance spectroscopy of sequential sera, examined ghrelin immunoreactivity, performed radioimmunoassays for glucagon like peptide-1 (GLP-1) and peptide YY (PYY) and electro-chemiluminescent cytokine analyses (tumor necrosis factor-α and interleukin-6; TNF-α, IL-6) on the sequential samples. Results: In those who gained ≥ 1.5kg (on average ∼5% of initial body weight), several metabolite levels were positively associated with weight change, in particular lactate which was 55% greater in patients with increased body weight during chemotherapy compared to those with stable weight during chemotherapy (p<0.01; the pre-specified primary end-point). A significant inverse relationship was also observed between levels of TNF-α and weight change group (ρ 0.476, p<0.05). Baseline lactate, alanine and body fat were all prognostic for weight gain (ROC AUC >0.77, p<0.05). No significant associations were observed between any other parameter and weight gain, nor any parameter and tumor burden, including cytokine and appetite peptide alterations. Conclusions: Metabonomics identifies pathways perturbed during early chemotherapy for breast cancer, and establishes a positive association between serum lactate, body fat, TNF-α and substantive weight changes during chemotherapy. Interventions that target these processes may be clinically useful in breast cancer.

No significant financial relationships to disclose.
Predictive factor for residual tumor after lumpectomy for close margins
Authors: Ozmen V. , Ozkan Gurdal S. , Muslumanoglu M. , Igci A. , Tuzlali S. S. , Ozcinar B. , Canbay E. , Kecer M. , Dagoglu T.
Published: August 2020

e11538

Background: It is critical to obtain clear margins to minimize local recurrence after breast conserving surgery(BCS). When re-excisions are performed, there is often no residual disease in the new specimen, calling into question the need for re-excision(s) or mastectomy. The aim of the present study was to identify factors predicting a histologically positive re-excision specimen. Methods: Our prospective breast cancer database was queried for all invasive breast cancer patients who underwent a re-excision lumpectomy for either close or positive margins after an attempt at BCS. Close margins are defined as ≤ 2 mm for invasive carcinoma and presence of ductal carcinoma in situ(DCIS). Clinicopathologic features were correlated with the presence of residual disease in the re-excision specimen. Results: Between February 1997 and August 2008, 2054 patients with early breast cancer underwent surgical treatment in our breast unit. 939(45.7%) of them had BCS. In 543 patients(26.4%), re-excision required due to close margins on the permanent section analysis of their initial surgical specimens. 186 patients(34.3%) had previous excisional biopsy in other clinics. Median age of 543 patients was 50 years. In 290 patients(53.4%), mastectomy was performed due to positive surgical margin or poor cosmetic results. There were no residual tumors in re-excision(65.6 %) or mastectomy(42.4%) specimens of patients. The factors associated with tumor positive re-excision specimen were, age ≤50 years(p=0.044), lymphovascular invasion (p=0.029), multifocality(p<0.001), tumor size >2cm(p=0.008), presence of DCIS(p=0.018), focal margin positivity(p<0.001), DCIS at resection margin(p=0.008) and node positivity (p<0.001). Conclusions: Most of our patients with early breast cancer had unnecessary re-excisions or mastectomy to obtain clear surgical margins. In subset group of patients, re-excision or mastectomy may not be required.

No significant financial relationships to disclose.
A decision tree to predict four or more positive axillary lymph nodes in breast cancer patients with positive sentinel node biopsy: Determining necessity for regional nodal irradiation in the absence of axillary dissection
Authors: Macrorie-Fairweather R. A. , Albuquerque K. , Yao K. , Sinacore J.
Published: August 2020

e11540

Background: Regional nodal irradiation (RNI) is indicated for breast cancer patients with ≥ 4 positive axillary lymph nodes (ALN). The need for RNI is unclear for women with T1–2 tumors and 1–3 positive sentinel lymph nodes (SLN) who don’t undergo axillary lymph node dissection (ALND). In an effort to guide clinician decision-making and potentially spare patients combined toxicities of ALND and radiation, the purpose of this study was to create a decision tree of clinicopathologic variables to predict patients with ≥ 4 positive ALN. Methods: We reviewed the records of 197 women with T1–2 tumors and 1–3 positive SLN. All patients underwent a complete ALND to determine the number of positive ALN. The patients were divided into 2 groups: < 4 or ≥ 4 positive ALN. Ten clinicopathologic predictive variables were identified for analysis: patient age, size of tumor, histological type, tumor grade, number of metastatic SLN, largest SLN metastasis size, detection method, estrogen receptor, Ki67 and lymphovascular invasion (LVI). The analysis used Chi-Square Automatic Interaction Detection (CHAID SPSS), a non-parametric, stepwise “regression tree” analysis, with Bonferroni adjusted p-values to create a decision tree. Results: 141 (72%) patients had < 4 and 56 (28%) had ≥ 4 positive ALN. Three variables were selected into the CHAID tree based upon maximum predictability: LVI, the number of metastatic SLNs, and largest SLN metastasis size. 100% of patients (N=42) had < 4 positive ALN if negative for LVI and had only 1 positive SLN with a metastasis size < 0.2cm (p-value < 0.0432). For patients with LVI (N=77), 13 of 14 (93%) had < 4 positive ALN if the SLN metastasis size was ≤ 0.2cm (p < .0014). The highest prevalence of ≥ 4 positive ALN were patients with LVI and a SLN metastasis size > 0.2cm. Conclusions: The CHAID analysis more accurately predicted patients with < 4 positive ALN compared to those with ≥4. The decision tree provides a new tool for the clinician to determine the necessity for RNI without ALND.

No significant financial relationships to disclose.
Fertility and pregnancy in patients under age 38 following chemotherapy for breast cancer
Authors: Katz D. , Mazeh H. , Divinsky L. , Temper M. , Ospovat I. , Salah A. , Hamburger T. , Galinsky D. , Uziely B. , Peretz T.
Published: August 2020

e11541

Background: Chemotherapy improves breast cancer outcome, but may impact fertility. Post chemotherapy fertility rates range between 10–90% among studies. Fertility post chemotherapy is most often assessed by rate of menstruation resumption- an indirect method of evaluating childbearing potential. It is noteworthy that future pregnancy is a woman's first concern not menses preservation. Variability in fertility rates along with limited data on post chemotherapy pregnancies led us to undertake this single institute retrospective study evaluating fertility and pregnancy post chemotherapy in ≤ 38 y old breast cancer patients. Methods: We reviewed medical records of 222 consecutive stage II-IIIB breast cancer patients diagnosed, treated and followed at Sharette Institute of Hadassah-Hebrew University Medical Center from 1990–2004. Inclusion criteria included age ≤ 38 years, ≥3 cycles of standard metothrexate or adriamycine based chemotherapy, metastasis-free 12 months post chemotherapy initiation or one year following GnRH analog withdrawal. Patients diagnosed with infertility prior to breast cancer diagnosis (data present for part of patients), bilateral oophorectomy or patients surviving ≤3 years from diagnosis were excluded. Patient pregnancy preference was not recorded. Fertility was defined as resumption of recurrent menses or pregnancy anytime during follow up. In case of recurrence, date of recurrence diagnosis was assigned as date of last follow up. Results: Cohort included 65 patients. Mean age 32.5±4 ys (20.3–38.5) Almost all patients (95.4%), 38 ys or younger, preserve menses following chemotherapy, and 33.9% become pregnant. Most of patients who did not conceive post chemotherapy (66.1%), were under a familial status not promoting pregnancy; 44% of all women who did not give birth post chemotherapy had at least 3 offspring at the time of diagnosis and 83% out of all women who did not have any offspring by the end of follow up were single. Conclusions: This data suggest that pregnancy potential may be even higher than our actual finding, since pregnancy is most probably not attempted by multiparous or most single patients, whom cultural constrains affect their decisions. It seems prudent to offer the subgroup of unmarried women fertility preservation.

No significant financial relationships to disclose.
A novel approach to identify sentinel lymph nodes using microbubbles and contrast enhanced ultrasound in preoperative breast cancer patients
Authors: Sever A. , Jones S. , Cox K. , Weeks J. , Mills P. , Fish D. , Jones P.
Published: August 2020

e11543

Background: In patients with early invasive breast cancer, surgical excision of sentinel lymph nodes (SLN) has been shown to be a safe and accurate first-line technique to stage the axilla. In animal models, superficial lymphatics can be imaged using ultrasound and intradermal microbubbles. We investigated the ability of contrast enhanced ultrasound to identify SLN preoperatively in breast cancer patients. Methods: We recruited 46 consecutive consenting patients with primary breast cancer. Pre-operatively; patients received periareolar intra-dermal injection of microbubble contrast agent, breast lymphatics were visualised by ultrasound and followed to identify putative axillary SLN. In 41 patients, we aimed to place guide-wires in the SLN. Patients then underwent standard operative tumour excision, SLN biopsy and histopathological analysis. Results: Microbubble enhancement identified putative SLN in 5 successive patients. In 36 patients, putative SLN were visualised and guide-wires deployed. Operative findings confirmed the wired lymph nodes (LN) were SLN. In 2 cases, SLN contrast enhancement failed but guide-wires were placed into prominent grey-scale imaged LN. These wired LN were not SLN. In 3 patients, the procedure failed. Contrast enhanced ultrasound correctly identified SLN in 36 of 41 patients (88%). Five patients were found to have metastasis. In all metastatic cases, SLN were correctly identified and localised with guide-wires pre-operatively. Conclusions: Microbubbles readily enter breast lymphatics and contrast enhanced ultrasound may represent a practical method to identify SLN. Improvements in percutaneous techniques may facilitate ultrasound guided SLN excision in the breast clinic and could reduce the numbers of patients requiring axillary surgery.

No significant financial relationships to disclose.
Correlation of tumor size on preoperative breast MRI and pathologic tumor size in Asian patients
Authors: Lee S. , Kim S. , Kang H. , Lee E. , Kim E. , Ko K. , Kwon Y.
Published: August 2020

e11546

Background: As many Asian patients want breast conserving therapy (BCT), use of magnetic resonance imaging (MRI) increase in preoperative diagnosis for breast cancer. But the impact of MRI on these patients has not been unclear. Methods: From January 2008 to July 2008, 423 patients underwent breast cancer surgery in National Cancer Center, Korea. We enrolled 357 patients consecutively in this retrospective study; 290 patients (non-MRI group) with preoperative mammography (MMG) and ultrasonography (US) vs. 66 patients (MRI group) with additional MRI to MMG, US and excluded 67 patients (42 patients with preoperative chemotherapy, 8 patients with ipsilateral recurrence, 17 patients whose MRI showed no residual lesion after excisional biopsy). We examined MRI effect on mastectomy rate, intraoperative conversion from BCT to mastectomy, positive margin rate in frozen specimen in both group. In MRI group, we evaluated the correlation between tumor size on US, MRI and pathologic tumor size. Results: Mean age of this study was 48.89 years (Non-MRI group: 50.70 years vs. MRI group: 46.33 years, p=0.001). The rate of mastectomy wasn’t different in both groups (Non-MRI group: 13.7% vs. MRI group: 19.4%, p=0.252). Intraoperative conversion to mastectomy was performed frequently in MRI group. (Non-MRI group: 1.7% vs. MRI group: 7.5%, p=0.023). But positive margin rate in frozen specimen was similar in both groups (Non-MRI group: 23.2% vs. MRI group: 34.0%, p=0.111). In MRI group, mean tumor size on MRI, US was 3.07cm, 1.98cm respectively. Mean pathologic tumor size was 2.67cm. The tumor size on MRI correlated strongly with the pathologic tumor size. The correlation coefficient was 0.732 (p=0.0001). But the tumor size on US didn’t correlate with the pathologic tumor size (p=0.066). In twenty nine patients whose MMG showed suspicious microcalcification, tumor size on MRI also correlated strongly with pathologic tumor size. The correlation coefficient was 0.693 (p=0.0001). But US didn’t show the correlation with the pathologic tumor size in these patients. Conclusions: Preoperative breast MRI didn’t give the impact on breast cancer surgery in Asian patients and could overestimate the size of tumor. But it could strongly correlate with the pathologic tumor size in Asian patients.

No significant financial relationships to disclose.
Is there a survival benefit with adjuvant chemotherapy for patients with stage I (T1N0) triple negative breast cancer?
Authors: Luu T. H. , Lau S. , Nelson R. , Ottochian M. , Garcia A. , Somlo G.
Published: August 2020

e11547

Background: Chemotherapy is the only systemic modality for patients with breast cancer lacking expression of estrogen, progesterone, and HER2 receptors (triple negative), a group comprising 15% of all breast cancers. The majority of such patients present with nodal metastases. The median time to distant recurrence is short: at 2.6 years, and median time to death is 4.2 years. (Dent R, et al. Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence, Clin Cancer Res 2007; 13(15) August, 2007). The benefit from proceeding with adjuvant chemotherapy for ≤2cm, node negative triple negative breast cancer remains undefined. Patients and Methods: A retrospective chart review was conducted to assess the benefit of adjuvant chemotherapy for overall survival for stage I (T1N0) triple-negative breast cancer treated from 1996 to 2006 at City of Hope and USC. ER, PR, and HER2 status (as assessed by fluorescent in-situ hybridization (FISH) or immunohistochemistry) were reviewed and confirmed. Overall survival was defined as time from date of diagnosis to date of death. All patients received standard surgery ± radiation. Results: A total of 100 stage I triple-negative breast cancer patients were identified. The median age at diagnosis was 56 (range 27–91). Of the 100 patients, 59 received adjuvant chemotherapy: 38 received anthracycline-based, 17 received non-anthracycline-based regimens and 4 were unknown. Median length of follow-up was 4.0 years. No difference in overall survival was found in patients who received adjuvant chemotherapy (p-value = 0.94). Similarly, there was no difference between patients who received non-anthracycline-based chemotherapy versus those given anthracycline-based chemotherapy (p-value=0.17). The group of patients who received adjuvant chemotherapy were younger (51.8 y.o versus 61.5 y.o (p=0.0004)) and had larger tumor size (13.6mm versus 10.2mm (p=0.0002)). Lack of statistical significance may be related to the limited sample size. Conclusion: We did not find a statistically survival benefit of adjuvant chemotherapy in 100 triple negative stage I breast cancer patients. Further studies are needed to clarify the role of adjuvant chemotherapy in this group of patients.

No significant financial relationships to disclose.
Effects of Shugan-Liangxue prescription combined with anastrozole (ANA) on bone metabolism of ovariectomy (OVX) rats
Authors: Li P. , Liu S. X.
Published: August 2020

e11551

Background: A randomized double-blind clinical trial has confirmed traditional Chinese medicine (TCM) Shugan-Liangxue prescription could relieve hot flashes in breast cancer with endocrine therapy. The purpose of this study was to observe the effects of TCM combined with ANA on serum estradiol (E2 ) level and bone metabolism. Methods: The postmenopausal animal model was successful after OVX and testified by vaginal smear method. Sixty 6-month SD rats were randomly divided into control, TCM, ANA, ANA+TCM, alendronate sodium (AL), and sham groups. After 16 weeks intragastric administration, the bone mineral density (BMD) of femur and lumbar vertebra were measured by dual energy X-ray absorptiometry. The serum E2, osteocalcin (BGP), and prostaglandin E2 (PGE2) were detected by radioimmunoassay and pyridinoline (PYD) was by ELISA. Results: Serum E2 level decreased in TCM, ANA, and ANA+TCM groups compared with the control (P<0.05, P<0.01, P<0.001), BMD had no significant difference compared with the control. In ANA+TCM group, BGP (bone formation index) increased, PYD (bone absorption index) and PGE2 declined significantly compared with ANA group (P<0.05, P<0.05, P<0.01). PYD decreased greatly in TCM and AL groups compared with the control (P<0.001, P<0.001). Conclusions: TCM combined with ANA decreased serum E2 level, but did not decline BMD of OVX rats. It could also elevate BGP and decrease PYD level in serum. It was possible that TCM combined with ANA could alleviate musculoskeletal pain through PGE2 decrease. The effect of TCM reducing PYD was similar with AL.

[Table: see text]

No significant financial relationships to disclose.
Weight gain after adjuvant TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy for node-positive breast cancer
Authors: Suh Y. , Oh S. , Song B. , Jung S.
Published: August 2020

e11552

Background: Despite of its proven therapeutic efficacy, TAC (docetaxel, Doxorubicin and cyclophosphamide) regimen as an adjuvant chemotherapy has some serious adverse effects such as fluid retention and neutropenia. Even though dexamethasone is known to be given for three days to the patients having TAC chemotherapy to prevent severe fluid retention, most patients have ironically been complaining of much weight gain more than 15% increase after the use of dexamethasone. We tried to determine abbreviated use of dexamethasone is better to decrease the extent of weight gain after TAC chemotherapy. Methods: Eighty node-positive patients between Jan. 2006 and Oct. 2007 were randomly assigned either into 24-hr (group A: 10 mg dexamethasone the night before TAC, and 10 mg dexamethasone (bid) were given for the day 1) or 72-hr dexamethasone premedication (group B) only after getting informed consent since all the protocols were reviewed by IRB. We compared the incidence of severe weight gain (more than 15%) on completion of six cycles in two groups. No patient was found to have heart or kidney problem before the commencement of chemotherapy. Results: Each group was comprised of 40 patients. All patients underwent 6 cycles. Mean age of each group was 48.5 (A) and 50.3 (B) years. The incidence of severe weight gain was 47.3 % in Group A, and 78.4 % in Group B. There was no difference in the duration of recovering from weight gain in both groups (A: 6.52 months vs. B: 7.02 months). No other hematologic complications seemed different between two groups. Conclusions: Though larger scale prosepctive randomized trials should be required to get the definitive conclusion on this matter, we think that current dexamethasone premedication may aggravate weight gain than to prevent it. If shorter schedule is as much effective as longer one, abbreviated and reduced dexamethasone premedication is more helpful for patients having TAC chemotherapy.

No significant financial relationships to disclose.
Trastuzumab and vinorelbine (TV) in early stages of breast cancer
Authors: Ferrario C. , Wong A. , Bouganim N. , Gao T. , Aloyz R. , Panasci L. C.
Published: August 2020

e11556

Background: HER-2+ breast cancers (BCs) have a higher relapse rate, even for early stages of disease. The combination of trastuzumab and vinorelbine (TV) displays a high degree of synergism both preclinically and in metastatic BC patients that typically tolerate TV remarkably well. Occasionally, patients refuse standard treatment with chemotherapy and trastuzumab because of toxic side effects. In our institution, some of these patients accepted to receive treatment with TV. Methods: We retrospectively collected data on patients with stage I-III BCs, treated with TV as the only chemotherapy regimen. Most patients received TV on a weekly basis (one week off for V every 3–4 weeks) for ∼6 months, followed by 6 more months of T only. Results: Between May 2003 and June 2008, 23 patients were started on weekly TV. Median age was 66. Five patients received TV as preoperative treatment for BCs with the following clinical stages: IIB (1); IIIA (1); IIIB (3). The other 18 patients were pathologically staged as: stage I (11); IIA (5); IIIB (2). All cancers were HER2+; 65% of patients also received hormonal treatment for ER/PR+ disease. 3 patients had been previously treated for BC, and received TV as “adjuvant” treatment after a local relapse. Only one of these patients had previously received chemotherapy, while none had received prior T. No pathological complete response was found at surgery after preoperative TV. TV was very well tolerated, with one patient developing febrile neutropenia, 4 patients grade 3–4 uncomplicated neutropenia, and no other grade 3–4 events. During therapy, 5 patients had an asymptomatic 10–20% drop in the LVEF (Grade 1). Follow-up MUGA scans at 1 year after TV so far failed to show any significant abnormality. At an average follow-up of 26 months, one patient died for non-BC related causes, and all the other 22 patients are disease-free. Conclusions: TV is safe and very well tolerated, with no significant cardiac toxicity in our patient population. Preliminary follow-up data suggest that TV may be an acceptable alternative (neo-)adjuvant therapy for patients refusing “toxic” chemotherapy. Further studies prospectively testing TV as adjuvant treatment should be considered for patients with stage 1A BC, for which no standard treatment is clearly defined.

No significant financial relationships to disclose.
Neoadjuvant dose-dense docetaxel, carboplatinum, and trastuzumab (ddTCH) chemotherapy for HER2 overexpressing breast cancer
Authors: Bayraktar S. , Bayraktar U. D. , Reis I. M. , Pegram M. , Welsh C. , Silva O. , Franchesci D. , Gomez C. R. , Hurley J.
Published: August 2020

e11557

Background: Neoadjuvant chemotherapy for locally advanced breast cancer was shown to improve the complete pathologic (pCR) and clinical response (cCR) as well as the disease free survival (DFS). Docetaxel, cisplatin, and trastuzumab given every 21 days in her2-positive breast cancer demonstrated a pCR rate of 23%. The concept of dose dense chemotherapy regimens has attracted much attention and we hypothesized that dose-dense regimen would further improve pCR, cCR and would maintain the safety profile while being a suitable regimen for outpatient administration. Methods: 48 patients with stage II/III HER2-positive breast cancer were prospectively enrolled on a clinical trial of a neoadjuvant regimen consisting of docetaxel 70 mg/m2 on days 1, 15, 29, and 43; carboplatinum at an AUC of 6 on days 1, 15, 29, and 43; trastuzumab 4 mg/kg on day 1 and 2 mg/kg weekly x 10 starting on day 8; peg-filgastrim 6 mg on days 2, 16, 30, and 44. Results: The median age was 50 years (range 30–78). 52% of patients were premenopausal, 63% and 22% were of Hispanic and African descent, respectively. Estrogen receptor was positive in 52% patients and median tumor size was 5 cm at the time of diagnosis. TNM stage distribution at presentation: T1 2%, T2 25%, T3 57%, T4 16%; N0 29%, N1 46%, N2 16%, N3 7%; M0 100%. pCR in breast; axilla; and both breast and axilla was observed in 19 of 44 patients (43.2%; 95% CI 28.3% - 59.0%); in 29 of 44 patients (65.9%; 95% CI 50.1% - 79.5%); and in 16 of 44 patients (36.4%; 95% CI 22.4% - 52.2%), respectively. No grade 4 or 5 toxicity occurred. The most frequent grade 3 toxicities were hand-foot syndrome (7%), neutropenia (4%), nausea/vomiting (2%), and bone pain (2%). Grade 2 cardiotoxicity was seen in 8% of patients and no grade 3 cardiotoxicity was observed. Conclusions: This neoadjuvant regimen was well tolerated and yielded a good pCR rate for this high risk group of patients.

No significant financial relationships to disclose.
Neoadjuvant trastuzumab in a sequential nonanthracycline-based regimen for patients with stage II-III breast cancer
Authors: Carillio G. , Aiello R. , Alì M. , Mazzola A. , Scandurra G. , Taibi E. , Chiarenza M. , Fallica G. , Caruso F. , Caruso M.
Published: August 2020

e11559

Background: Recently, some studies have demonstrated benefit from adding trastuzumab to neoadjuvant anthracycline-containing chemotherapy for HER2-positive breast cancer patients. However, trastuzumab can increase cardiotoxicity, particularly when combined with anthracyclines. This represents a relevant issue for patients who usually need to receive radiotherapy or further systemic treatment. Methods: In the late 2007 we started a phase II study for testing activity and safety of neoadjuvant trastuzumab in association with sequential chemotherapy, based on favourable in vitro combination index, proven efficacy, and moderate cardiotoxicity. Weekly trastuzumab for 18 weeks was combined with cisplatin 80 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1+8 q3w for 3 courses, followed by docetaxel 100 mg/m2 q3w for further 3 courses. Peg- filgrastim was administered to prevent neutropenia. Adjuvant trastuzumab q3w was planned for one year. Eligible patients had stage II-III core-biopsied breast carcinoma with overexpressed or amplified HER2/neu. Adequate cardiac function with LVEF ≥ 50% was required for trastuzumab administration. Primary end-point was pathologic complete responses (pCR) rate. The study is registered on the European Clinical Trials Database. Results: Among 17 enrolled patients, 15 were evaluable for primary end-point. Median age was 50 years (range 23–70), stage II and III breast cancer in 4 and 13 patients, respectively, with 4 cases of stage IIIB (2 T4b and 2 T4d), and 2 women with synchronous bilateral cancer. Neoadjuvant regimen yielded 6/15 pCR (40%). Only 3/12 patients treated with lymphadenectomy due to initial clinically suspected axillary nodes presented pN+, but none of them had more than 3 positive nodes. In two cases we observed a total pCR, involving both primary tumor and axillary nodes. Treatment was safe, with only 2 events of short G4 non febrile neutropenia on 97 chemotherapy cycles. Alopecia was moderate at the end of treatment, without any case of complete hair loss. No significant cardiac dysfunction was recorded during the neoadjuvant therapy. Conclusions: The present sequential non anthracycline-based chemotherapy associated with weekly trastuzumab showed promising results in neoadjuvant setting.

No significant financial relationships to disclose.
Pathologic complete response (pCR) in HER2 positive breast cancer to sequential FEC 100-docetaxel (D) plus trastuzumab (T) neoadjuvant chemotherapy (NCT)
Authors: Chollet P. J. , Dubray P. , Durando X. , Abrial C. , Nayl B. , Mouret-Reynier M. , Pomel C. , Bellière A. , Lemery S. , Penault-Llorca F.
Published: August 2020

e11560

Background: Trastuzumab plus chemotherapy has become the standard of care for Her-2-positive breast cancer. Recent trials have shown higher pCR rates in Her2-positive tumors with trastuzumab-driven combinations (Buzdar, JCO 2005; Coudert, Ann Oncol, 2006). The purpose of this study was to review efficacity of sequential FEC followed by D+T. Methods: 21 patients (pts) with Her2-positive breast cancer (defined as either immunohistochemical 3+ or fluorescence in situ hybridization-positive) from June 2006 to September 2008 with breast cancer received 3 cycles (c) of FEC 100 ( epirubicin 100 mg/m2 + 5-fluorouracil and cyclophosphamide 500mg/m2) followed by 3 c of D (100mg/m2) every 3 weeks +T 2mg/kg weekly or 6mg/kg every 3 weeks (9 weeks of T). pCR was defined according to Chevallier's (Am J Clin Oncol, 1993) as level 1 and 2 and to Sataloff's classification (J Am Coll Surg, 1995) as grade A. A clinical, mammography and ultrasound breast evaluation was performed at baseline, after 3 or 4 c and before surgery. Cardiac evaluation (ejection fraction) was performed at baseline, after 3 c of FEC, before surgery and every 3 months after. Results: Median age was 52.1 years [27–71]. Median diameter of the tumors was 45 mm [10–160]. All pts had a ductal carcinoma. 5 pts had inflammatory breast cancer. 1 pts were grade I SBR, 13 grade II SBR, 6 grade III SBR and 1 unspecified. 5 tumors were HR+, 15 HR- and 1 unspecified. After FEC 100 x3, a clinical partial response (PR) was obtained in 4 pts (19%). After completion of NCT,clinical objective response rate was 95.2%: 13 pts had a complete response and 7 pts a partial response. 13 pts (62%) underwent breast-conserving surgery. 10 pts (47.6%) achieved pCR using Chevallier's classification (1 HR+ and 9 HR-) and 12 pts (57.1%) using Sataloff's classification (2 HR+ and 10 HR-). At the time of the analysis for cardiac evaluation, 8 pts continued to receive adjuvant T. 1 pt was lost for follow-up. 5 pts (25%) had an asymptomatic drop of ejection fraction greater than 10%. Conclusions: This regimen with only 9 weeks preoperative trastuzumab resulted in a high rate of pCR in Her2-positive tumors, without clinical cardiac events until now.

No significant financial relationships to disclose.
Bone density changes during adjuvant aromatase inhibitor treatment in breast cancer patients: Single center experience
Authors: Almatari M. , Moe M. , Ali P. , Willshaw P.
Published: August 2020

e11565

Background: Adjuvant aromatase inhibitors (AI) therapy in breast cancer accelerates bone loss resulting in increased incidence of fracture. We evaluated the effect of AI on bone density changes among breast cancer patients. Method: A total of 85 patients who had adjuvant AI for more than 24 months and 3 Dual energy X-ray Absorptiometry (DXA) scans were included in this study. Annual bone density change was calculated and correlated with various risk and prognostic factors. Results: Adjuvant AI was given in up-front (50), sequential (15) and extended adjuvant (17) therapy settings, with a median duration of 31 months. Intervals between scans varied from 6 - 33 months (median = 13 months), 63 patients had baseline DXA scans undertaken within 6 months from start of AI. Bisphosphonate was prescribed to 35 patients during AI therapy according to local practice. Changes in bone density according to WHO classification is shown in the table. Annual bone density change in the spine at 2nd scan was (-9.2% to +11%, mean = -0.89±4.11), after 3rd scan, (-11.7% to +10.7%, mean = 0.021±3.84). In the group of patients who had adjuvant chemotherapy (59 patients), significant bone loss was seen in the patients who did not have bisphosphonate (n=39), (-0.011 in BMD, Mean=0.88±0.02) compared to those who had bisphosphonate (n=20), (0.036 in BMD, Mean=0.93±0.02). In the patients who did not have chemotherapy (n=26), no bone loss was seen whether bisphosphonate was used or not. No clinical bone fracture was reported among patients who had osteoporosis at baseline. Conclusions: The patients who had chemotherapy are more likely to lose bone density and close monitoring is required for bisphosphonate therapy. Bone loss is more significant in the lumbar spine compared to the hip. Following intervention with bisphosphonate, the rate of bone loss was reduced, and as a result only 2.3% of patients developed osteoporosis during AI treatment. AI can be safely given from the bone health point of view with the appropriate use of bisphosphonate.

[Table: see text]

No significant financial relationships to disclose.