bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognosis value of hormonal and HER2 receptors on overall survival (OS) and disease-free interval (DFI) in metastatic breast cancer (MBC)
Authors: Francis L. , Olivier T. , Frédérique P. , Catherine A. , Marie-Ange M. , Ines R. , Xavier D. , Pierre G. , Hervé C. , Philippe C.
Published: March 2020

1077

Background: In MBC, positive HR constitute a favourable prognostic factor and predict response to an hormonal therapy. Conversely HER-2 overexpression is an adverse prognostic factor associated with a more aggressive tumor. In this retrospective study we analysed overall survival (OS) and disease-free interval (DFI) of three phenotypes: HR-/HER-2- (triple negative); HR+/HER-2- (luminal) and HER-2 overexpression (HER-2+). Methods: We evaluated 511 patients with a MBC treated at Centre Jean Perrin from 1973 to 2006. A comparative lecture of oestrogenic, progestative and HER-2 receptors was performed by IHC. At present, HR and HER-2 status were re-evaluated on 166 initial tumor sample of this data base by two pathologists (study currently ongoing). Median age of patients was 54.8 years. 120 (23.6%) patients were directly metastatic (M1), 391 (76.4%) relapsed distantly (M0). Metastatic patients received a median number of 2 lines of chemotherapy (range, 0–14) and/or a median number of 1 line (range, 0–8) of hormonotherapy. 92 (55.4%) patients had a luminal phenotype, 48 patients (28.9%) were HER-2+ and 26 patients (15.7%) were triple negative. Results: Among these 166 tumors, OS was significantly different between these three populations (p=0.00056). DFI variation was not signicant (p=0.083). These data showed that: - Luminal phenotype had the better OS (median survival of 36.5 months) and DFI (51.09 months) - HER-2+ phenotype (33 of 48 patients were treated with trastuzumab from 1999) had an intermediate prognostic on OS (median survival of 31.1 months) and DFI (42.2 months) - Triple negative phenotype had a poor prognostic on OS (median survival of 12.8 months) and the worse DFI (32.64 months) Conclusions: In metastatic breast cancer, luminal phenotype patients had the best OS; HER-2+ phenotype (treated by herceptin) had an intermediate OS, and triple negative phenotype had the worse OS.

No significant financial relationships to disclose.
Influence of letrozole on plasma estrogen levels in postmenopausal patients with metastatic breast cancer and the effect of estrogen levels on response rates
Authors: Zidan J. , Abzah A. , Chetver L. , Basher W. , Shneider J. , Tamam S.
Published: March 2020

1078

Background: The aromatase inhibitor (AI) letrozole and other members of this treatment group are very effective in the treatment of postmenopausal women with breast cancer. AIs markedly reduce estrogen levels in postmenopausal women by inhibiting aromatase. At menopause estradiol levels are about 25 pmol/l. Estradiol levels are higher in plasma of women with breast cancer as compared with women with no breast cancer. The purpose of this prospective study is to evaluate estradiol levels before and during letrozole treatment and the effect of primary estradiol levels and their decrease on response rate. Methods: Letrozole 2.5 mg/day orally was given to 50 patients (pts) with metastatic and locally advanced breast cancer (MBC). All pts had measurable disease. Overnight fasting clotted blood samples used for assessment of serum levels of estradiol at baseline and after 3, 6 and 12 months. Estradiol levels were compared to clinical response in this single stage study. Results: Mean age was 56 years (range 46–89 y). Mean years from menopause to starting letrozole was 9 years.12% of pts received previous hormonotherapy and and 30% received chemotherapy for their metastatic disease. Estradiol levels decreased from a mean of 40 pmol/l before letrozole to 40 pmol/l and <40 pmol/l in 19 pts (38%). No difference in estradiol depression rate was found between the 2 groups. In the first group (estradiol >40 pmol/l) objective response rate was 48%: 4 complete responses (CR) and 11 partial responses (PR) out of 31 pts, 12 pts had stabilization of the disease (SD). In the second group 3 pts had CR, 5 had PR: objective response rate of 42% (8/19), and 42% SD. There is a trend (not significant) for higher response rate in pts with higher estradiol levels at the beginning of treatment. Conclusions: Letrozole was found to cause very high estradiol suppression and high response rates in postmenopausal women with advanced breast cancer. A trend was found for higher response rates in pts with higher estradiol levels at baseline although difference was not significant. This is the first study to address this issue.

No significant financial relationships to disclose.
Kinetics of CEA and CA15–3 correlate with response in patients undergoing chemotherapy for metastatic breast cancer
Authors: Stieber P. , Laessig D. , Heinemann V. , Untch M. , Kahlert S. , Nagel D.
Published: March 2020

1087

Background: The aim of this retrospective analysis was to determine the correlation between tumor marker kinetic (TMK) like CEA and/ or CA 15–3 and imaging during of MBC pts. Methods: TMK (CEA, AxSYM, Abbott; CA 15–3, Elecsys, Roche) were evaluated in MBC pts at the beginning of palliative chemotherapy (pre-treatment value = A), after 20–30 days (1st intermediate value = B), after 40–60 days (2nd intermediate value = C) and at the time of staging with imaging techniques (D). Response to treatment was assessed by UICC criteria. Two criteria for progressive and two for non-progressive disease based on TMK were established. The 1st criterion for progression required that the increase from A to C had to be >25 %, and the increase per day from A to C had to be greater than the increase from A to B. The 2nd criterion for progression required that D should be >25% than A and an increase of C to D was required. The 1st criterion for non-progressive disease required that the decrease from A to C had to be > 25% and C < B. The 2nd criterion for non-progressive disease required D <25% than B and D < C. Results: 54 (70%) pts showed a correlation of TMK and imaging results. In 10 (13%) pts no correlation was obtained, and in 13 (17%) pts no biochemical statement was possible because of divergent TMK. Using our criteria a sensitivity of 70.2 % was reached. Conclusion: We could show a correlation between TMK and imaging results. After validation in a prospective trial using our criteria in clinical practice could improve therapeutic monitoring and reduce radiation exposure in pts with MBC.

No significant financial relationships to disclose.
Multi-drug resistance and breast cancer: A meta-analysis of MDR1 and its functional significance
Authors: Trock B. , Leonessa F. , Clarke R.
Published: March 2020

11010

Background: The clinical significance of MDR1 as a mechanism of multidrug resistance in breast cancer has not been established. We conducted a meta-analysis examining MDR1/gp170 in breast cancer, significantly updating a meta-analysis we performed in 1997. Methods: Published papers on MDR1/gp170 and breast cancer were identified by searching literature databases and bibliographies of published papers. Pooled relative risks (RR) for association between MDR1/gp170 expression and clinical outcomes were estimated with the Mantel-Haenszel method. Results: 84 studies were included in analysis: 63 measured MDR1/gp170 expression, 21 measured response to chemotherapy, 11 used sestamibi imaging, and 11 evaluated multidrug resistance reversing agents. MDR1 expression was detected in 45.9% of breast tumors prior to treatment and 66.8% of tumors after treatment (p<0.0001). There were no significant differences in gp170 expression by antibody type (p=0.567). In 11 studies, MDR1/gp170 expression after chemotherapy was associated with a significant risk of non-response, RR=1.79 (95% CI=1.35, 2.35), p<0.0001. This effect was lower in 13 studies with MDR1/gp170 assessed prior to chemotherapy, RR=1.28 (1.06, 1.55), p=0.009. Only 7 of 16 studies showed significant associations with decreased progression-free or overall survival. Of 11 sestamibi imaging studies, 10 showed a significant association between shorter retention and higher levels of MDR1/gp170, suggesting active protein pumping of contrast agent. None of 11 studies of multidrug reversing agents found >25% of refractory patients improving to partial clinical response, but most studies did not confine treatment to patients with MDR1/gp170 expression. Conclusions: This meta-analysis includes nearly 3 times as many studies as our 1997 analysis. MDR1 is expressed in approximately half of breast cancer patients, and is induced by chemotherapy. MDR1 after chemotherapy is associated with RR=1.8 for failure to achieve a clinical response, and RR=1.3 without induction by chemotherapy. Sestamibi gives the strongest support for active efflux of agent by gp170, but studies with MDR reversing agents have shown little success, which may partly reflect poor study design.

[Table: see text]
Surgeon specialization and patient satisfaction with breast cancer treatment
Authors: Waljee J. F. , Hawley S. T. , Alderman A. K. , Morrow M. , Katz S. J.
Published: March 2020

11012

Background: Experience and practice setting vary greatly among surgeons who treat patients with breast cancer. Yet, little is known about how these factors influence patient outcomes such as patient satisfaction with aspects of care. Methods: All women with DCIS and a 20% random sample of women with invasive breast cancer diagnosed in 2002 and reported to the Detroit and Los Angeles metropolitan SEER registries were identified and surveyed shortly after receipt of surgical treatment. Attending surgeons were identified primarily using pathology reports and mailed a survey. The final sample contained complete dyad information for 64.6% of patients (n=1,539) and 69.7% of surgeons (n=318). Logistic regression was used to examine the associations between surgeon specialization (% of practice devoted to breast disease) and treating hospital cancer program status (no program, American College of Surgeons approved cancer program, or NCI cancer center) with four domains of patient satisfaction: 1) the surgical decision, 2) decision-making process, 3) surgeon-patient relationship, and 4) surgeon-patient communication, adjusting for patient and surgeon demographics and disease stage. Results: 34.5%, 32.5% and 33.0% of patients were treated by surgeons who devoted <30% (low volume), 30%-60% (medium volume), and >60% (high volume) of their practice to breast disease. Compared to patients who were treated by low volume surgeons, patients treated by medium or high volume surgeons were more satisfied with the decision making process (medium volume: OR=1.2, 95%CI 0.8–1.7, high volume: OR=1.8, 95% CI 1.1- 2.8, p=0.036) and more satisfied with the surgeon-patient relationship (medium volume: OR=1.1, 95% CI 0.7 - 1.7, high volume: OR=2.1, 95% CI 1.1–3.7, p=0.053). Similar trends were observed for the other domains of satisfaction. Treatment setting was not associated with patient satisfaction after controlling for other factors. Conclusions: Surgeon specialization, but not treatment setting, was associated with patient satisfaction. Examining the processes underlying these associations could inform strategies to improve the quality of breast cancer care.

No significant financial relationships to disclose.
Validation of the 2005 St. Gallen risk categories for operated breast cancers using a database from a regional cancer center in Hong Kong
Authors: YAU T. , Soong I. , Chan K. , Chang A. , Sze H. , Yeung R. , Tung R. , Lau S. , Lee A.
Published: March 2020

11019

Background: Breast cancer risk categories were revised by the St Gallen international expert consensus meeting in 2005. This study was to validate their application in Hong Kong. Methods: The clinical outcomes of female breast cancer patients presented from 1994 to 2002 were retrospectively analyzed. Patients with non-invasive cancers, unknown HER-2 status, unclear primary (T) or nodal (N) stage, distant metastases at presentation, induction chemotherapy or no definitive surgery were excluded. Results: 902 breast cancers were eligible for further analysis. Adjuvant radiotherapy, hormonal therapy and chemotherapy were given in 74%, 68% and 56% of patients respectively. The median follow-up was 5.4 years (range 0.3- 12.5 years). The risk categories were highly predictive of all survival outcome parameters (p<0.00005; Table). In the intermediate risk category, node-negative patients with endocrine responsive/ responsiveness uncertain tumors had better 5-year distant failure-free survival (DFFS) than the rest with either 1–3 positive nodes or endocrine non-responsive tumors (95% vs 89%, p=0.005). Patients with 1–3 positive nodes and HER-2 overexpressed tumors were classified as high risk but their 5-year DFFS was similar to that in the worse subgroup of intermediate risk and significantly better than those with ≥4 positive nodes (89% vs 65%, p=0.0001). Further analysis showed that HER-2 overexpression had adverse impact on DFFS of patients with ≥4 positive nodes (hazard ratios (HR) 1.78; 95% CI, 1.12 - 2.84; p=0.015) but not on those with ≤ 3 positive nodes (HR 1.15; 95% CI, 0.67 - 1.97; p= 0.61). Conclusions: The 2005 St Gallen risk category is a useful clinical tool but we cannot confirm the adverse impact of HER-2 overexpression in our patients with ≤ 3 positive nodes.

[Table: see text]

No significant financial relationships to disclose.
High-dose sequential chemotherapy (HDSC) with peripheral blood progenitor cells (PBPC) support for high-risk breast cancer (BC)
Authors: Sabbatini R. , Da Prada G. A. , Frassineti G. L. , Aietta M. , Pedrazzoli P. , Maur M. , Zambelli A. , Giovannini N. , Siena S. , Ponchio L. , Conte P. F.
Published: March 2020

11026

Background: Recent reports suggest that intensified adjuvant chemotherapy with stem cell support improve disease free (DFS) and overall survival (OS) in subgroups of patients with high risk BC. We retrospectively analyzed the efficacy, safety and feasibility of a program of HDSC with PBPC support (according to the Milan protocol, ASCO 2001) in patients with BC at high risk of recurrence Methods: Between February 1995 and January 2001, 201 non-consecutive patients with more than 3 positive axillary nodes at surgery, median age 46 (range 27–62), has been evaluated. Median number of involved nodes was 15 (range 3–48), 38% and 49% pts had ER and PgR negative tumors, respectively. Fourty-sevent percent of pts had tumors with a high proliferative activity. HDSC consisted of sequential administration of cyclosphosphamide 7 g/m2 (day 0) plus filgrastim 5 μg/kg s.c. daily and stem cell collection, methotrexate 8 g/m2 plus vincristine 2 mg/m2 (day +16), and two consecutive courses of epidoxorubicin 120 mg/m2 (days +23 and + 38) plus filgrastim 5 μg/kg s.c. daily. Myeloablative therapy (day +58) consisted of thiotepa 600 mg/m2 and melphalan 160 mg/m2 plus PBPCs and filgrastim 5 μg/kg s.c. daily. Results: Three pts discontinued the program permanently because of toxicity. A median of 9,35x106/kg (range 3.35–35.62) CD34+ cells was infused. Engraftment for neutrophils (> 500/μl) and platelets (> 20.000/μl) was observed a median of 9 days (range 7–17) and 10 days (range 7–18) after PBPC infusion, respectively. No treatment-related deaths were recorded. After a median follow-up of 79 months, 108 (54%) pts are disease- free. Ninety-three patients experienced disease recurrence [9/93 (10%) pts had loco regional disease recurrence and 84/93 (90%) pts distant recurrence], of whom 58/93 (63%) have died. Five-year DFS and OS from the start of treatment are 55% and 71%, respectively. No poor marrow function, myelodysplastic syndrome or secondary tumors were observed. In 2-sided log-rank tests, hormone-receptor status and the number of tumor-positive axillary lymph nodes were significant prognostic factors for DFS. Conclusions: Our results confirm that HDSC is a safe procedure and is associated with favorable outcome in patients with high-risk BC.

No significant financial relationships to disclose.
Retrospective analysis of clinico-pathological features and outcomes of 2,686 hormone receptors-positive breast cancer (HR+) patients in a consecutive mono-institutional series
Authors: Ferro A. , Triolo R. , Caffo O. , Barbareschi M. , Leonardi E. , Frisinghelli M. , Caldara A. , Ambrosini G. , Lucenti A. , Galligioni E.
Published: March 2020

11036

Background: Clinico-pathological patterns, management and outcomes of HR+ vs HR- have been evaluated in a retrospective study. Methods: A series of 2686 BC patients (pts), treated at our institution from 1988 to 2000 with known immunohistochemical receptor status was investigated. Correlation between HR status and tumour size (T), nodal status (N), grading (G), mib-1, HER-2 and p53 and was evaluated by χ square test. Statistical analysis was performed to test the interaction between HR status and Disease Free Survival (DFS) and with specific and overall survival, using the log-rank test. Results: Among 2686 patients, 467 HR- (17%) and 2219 (83%) HR+ (364 pre and 1855 postmenopausal) were observed, with 1586 ER+PgR+, 555 ER+PgR-, 78 ER-PgR+. Pts with positive HR status showed a statistically significant correlation with lower T, G, mib-1, HER-2 and p53 expression.Chemotherapy was administered to 681 HR+BC (31% ) and to 301 HR-BC (65%), according to stage, age, and G. Tamoxifen based endocrine therapy was administered to 1167 HR+BC (53%) (associated to chemotherapy in 428 and alone in 739 pts). At a median follow up of 108 months, 499 relapses occurred in HR+ (22%) , and 141 in HR- pts (30%), with a 5,10, 15y DFS of 83%,72%, 62% in HR+ and 72%,66%, 57% respectively in HR- pts. More frequent sites of relapse were soft tissue (46%) and bone (35%) in HR+ and soft tissue (50%) and visceral (30%) in HR- pts. Seven hundred sixty pts have died: 576 HR+ (26%) and 184 HR- (39%), with a 5, 10, 15y specific survival of 90%, 84%, 75% which was significantly superior to the 78%, 73%, 69% respectively of HR-. However, considering that 230 HR+ and 44 HR- pts died without relapse, the 5,10,15y overall survival was 90%, 75% 61% for HR+ and 78%, 67%, 60% respectively for HR-. It appears therefore that the specific survival advantage in early years in favour of HR+ is progressively reduced by non specific mortality in late years which results in similar 15 y OS rates among HR+ and HR- pts. Conclusions: Our series appear to confirm the relationship between HR+ status and other more favourable clinical-pathological features, although long term OS is not apparently affected.

No significant financial relationships to disclose.
Randomized phase II trial of three dosing schedules of nanoparticle albumin-bound paclitaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer: An initial interim safety report
Authors: Conlin A. K. , Seidman A. D. , Moynahan M. E. , Traina T. , Mace J. R. , Meiri E. , Bach A. , Edwards C. , Hudis C. A.
Published: March 2020

1104

Background: Nanoparticle paclitaxel (NP) at 260mg/m2 every 3 weeks (q3wk) is more effective than standard paclitaxel (P) (Gradishar et al, JCO 2005). Weekly, uninterrupted administration of P is superior to q3wk P in MBC (Seidman et al, Proc ASCO 2004). When added to weekly P as 1st-line therapy for MBC, bevacizumab (B) improves response rate and progression-free survival (Miller et al, Proc ASCO 2005). We initiated a randomized phase II trial of NP given at 260mg/m2 q3wk (arm A) vs. 260mg/m2 q2wk with filgrastim (arm B) vs. 130mg/m2 weekly, all with B, as 1st-line therapy for patients (pts) with HER2- MBC. Methods: 66 of planned 225 pts have enrolled. After 31 pts had been randomized and treated, investigators concerned about possible differential neurotoxicity requested this early interim safety analysis. Median age is 54 (range 40–78). 83% are post-menopausal and 100% have visceral dominant disease. 68% had prior adjuvant or neo-adjuvant chemotherapy; 35% with taxanes. Results: With 170 cycles delivered (median: 4, range 1–15) 10 dose reductions have been necessary for NP (1 in A, 5 in B, 4 in C). No hypersensitivity reactions or dose interruptions have occurred for NP; 3 doses of B have been held due to hypertension. Significant preliminary antitumor activity has been noted in all arms. One grade 4 toxicity occurred in arm C, hyperglycemia. 15 grade 3 toxicities have been reported across all arms. Pts on arm A have experienced 3 grade 3 toxicities (30%): fatigue, neutropenia, and arthralgia with no grade 3 neurotoxicity. Pts on arm B have had 7 grade 3 toxicities (58%) with 3 pts experiencing grade 3 sensory neuropathy (25%) and others experiencing fatigue, neutropenia, anemia, esophagitis, dyspnea, and ataxia. 5 arm C pts experienced grade 3 toxicities (56%) including diarrhea, dehydration, mucositis, neutropenia, hypokalemia; 2 pts have had grade 3 sensory neuropathy (22%). Conclusions: This early safety analysis does not detect any statistically or clinically significant differences in grade 3 toxicity and all arms continue to accrue. The next protocol-specified safety analysis is expected in early 2007, with mature safety data for 60 pts. Updated results will be presented.

[Table: see text]
Overnight fasting serum cholesterol, HDL, LDL and triglycerides levels and bone mineral density (BMD) values during adjuvant letrozole in daily practice.
Authors: Fontaine C. , Huizing M. , Dewaele A. , Vandenbossche K. , Vermey J. , Schallier D. , Geurs F. , Neyns B. , Degreve J.
Published: March 2020

11040

Background: Background: Randomized clinical trials (RCT’s) have demonstrated a superiority of adjuvant aromatase inhibitors (AI’s) over tamoxifen (TAM) in disease free survival and overall survival, immediately postoperatively, in cross-over or extended setting in hormone receptor positive BC. In these studies AI’s were associated with increased bone demineralization and a rise in non- fasting serum cholesterol. Patients and methods: The tolerance for adjuvant letrozole was reviewed in 185 postmenopausal women with hormone receptor-positive early BC including fasting cholesterol levels and bone mineral density (BMD) values. Results: 121 patients (pts) received first-line adjuvant letrozole and 64 pts were crossed over from TAM. Median follow-up was 26 months (15–63 mths). Median age was 56 yrs (37–85y). Median time on letrozole was 23 months. Forty three of the 185 (24 %) of the pts discontinued the adjuvant therapy with letrozole (after a median duration of treatment of 5 months (1wk-30mths)), because of intolerance (83.7%)and PD in 16.3%. Median overnight fasting serum cholesterol levels did not change significantly (p=0.4) over a 2 year observation period from (203.5 mg/dl (131–342)) baseline to (205.5 mg/dl (151–330)) follow-up in 32 evaluable (14/32 pts prior TAM) pts. Median HDL levels rose from 65.5 mg/dl (38–107) to 70 mg/dl (38–103) (p=0.03) after 2 years, but LDL levels did not rise significantly. In the contrary triglycerides levels decreased from 122.5 mg/dl (48–238) to 105 mg/dl (47–285) (p=0.01). Despite the use of upfront biphosphonates in 1/3 of the pts, loss of BMD was significant for the lumbar spine after 2 years in 22 evaluable (8/22 prior TAM) pts (median T-score decreased from minus 0.3 to -0. 45, p=0.02), but not for the hip. Conclusion: Adjuvant letrozole did not significantly increase overnight fasting serum cholesterol levels in daily practice. Adjuvant letrozole was associated with a significant rise in HDL levels and a significant decrease in triglycerides levels after 2 years of therapy. Loss of BMD was observed in concordance with results from RCT’s. Adjuvant letrozole had to be discontinued prematurely because of tolerance issues in 20 % of the pts.

No significant financial relationships to disclose.
How important is the axillary nodal status for adjuvant treatment decisions at a breast cancer multidisciplinary tumor board? A survival analysis
Authors: Reimer T. , Fietkau R. , Markmann S. , Stachs A. , Gerber B.
Published: March 2020

11041

Background: Postoperative tumor board recommendations for breast cancer are mainly based on patient characteristics and tumor parameters such as size, histologic grade, lymphovascular invasion (LVI), hormone receptor and HER2/neu status. In the era of potential avoidance of axillary surgery in clinically node-negative patients we evaluate the impact of pathologic nodal status for adjuvant treatment decisions. Methods: The postoperative tumor board records of 207 consecutive breast cancer patients over a 1-year period were rediscussed without knowledge of pathologic nodal status. Differences between the two board recommendations for each patient were classified as major (chemo- and/or radiotherapy: present/absent) or minor (different chemotherapeutic protocols) discrepancies. The disease-free and overall survival rates among subgroups with different recommendations were calculated using Adjuvant! Online tool. The binary logistic regression was performed to analyze the impact of factors for prediction the major discrepancy subgroup. Results: The tumor board without information of pathologic nodal status resulted in treatment changes in 72 of the 207 patients studied (34.8%). Major discrepancies were observed in 37 patients (17.9%) leading to a complete shift of postoperative management. Disease-free and overall survival rates were not significantly different due to a balanced over- and undertreatment in this subgroup (21 cases with under-, 16 cases with overtreatment). The major discrepancies were related to LVI (P=0.001), postmenopausal status (P=0.047), and positive hormone receptor status (P=0.17) in the univariate setting. LVI was an independent parameter to predict the subgroup with major discrepancies performing a multivariate analysis (P=0.006; RR=4.5 [95%CI: 1.5–13.4]). Conclusions: The knowledge of pathologic nodal status is important for postoperative chemotherapy and postmastectomy radiotherapy indications. There is a risk for one third of all patients when avoiding axillary surgery to get an adjuvant therapy which differ from the current treatment guidelines. It is mandatory to know the nodal status for breast tumors with LVI.

No significant financial relationships to disclose.
To analyze the efficacy, tolerability, toxicity profile, quality of life and pharmaco-economics of adjuvant TAC compared to FAC regimen in hormone receptor-positive breast cancer with more than four involved lymph nodes
Authors: Batra U. , Bapsy P. P. , Saini K. V. , Jain A. K. , Atilli A. V. , Lokanatha D. , Babu K. S. , Sanjeevan K. S. , Devaraju C. J. , Anupama G.
Published: March 2020

11043

Aim: To analyze the efficacy, tolerability, toxicity profile, quality of life, survival rates and pharmaco-economics of TAC vs. FAC in women with ER/PR positive breast cancer and >4 involved lymph nodes. Methods: 100 patients with >4 node-positive breast cancer were randomly assigned to receive either 6 cycles of taxane-based (TAC) or anthracycline-based (FAC) adjuvant chemotherapy. All the patients received adjuvant radiotherapy and hormonal therapy after completion of chemotherapy. The primary end point was to assess disease-free survival (2 years), toxicity profile, QOL and to analyze the pharmaco-economics of both therapies. All patients completed EORTC QLQ 30, BR 23 questionnaire before randomization and before every cycle of chemotherapy. Pharmaco-economic feasibility was determined using cost of drugs, duration of hospital stay, laboratory investigations, management of complications and loss of wages. Treatment: The treatment (dose in mg/m2) was as follows: TAC: docetaxel 75, doxorubicin 50, cyclophosphamide 500; CAF: 5 flourouracil 500, doxorubicin 50, cyclophosphamide 500. Results: The patient demographics and primary tumor characteristics were comparable in both the arms. Taxane- based regimen was associated with decreased global QOL and physical function. The cost of TAC regimen was 25 times more than FAC regimen. Conclusion: Although TAC regimen had longer DFS as compared to FAC, it was associated with a higher incidence of side effects and increased duration of hospital stay. Further, high cost precludes its wide-spread use, and FAC regimen still continues to be the first choice treatment of high-risk node and receptor-positive breast cancer in a third world country like India.

[Table: see text]

No significant financial relationships to disclose.
Hormone replacement therapy (HRT) in women with previously treated primary breast cancer: Update XIII
Authors: Bluming A. Z.
Published: March 2020

11044

Background: To assess the incidence of contralateral or recurrent breast cancer among women prospectively treated with HRT after initial breast cancer diagnosis. Methods: A community-based, prospective, single-arm, pilot study of HRT among 246 women with previously treated primary breast cancer. Results: Median duration of HRT is 89+ months (range 12+ -173+). Median interval from initial surgery to initiation of HRT is 52 months (range 2–361 months). Follow-up to date is 100%. Actuarial disease-free survival (DFS), disease-specific survival (DSS), & median duration of HRT by stage are listed in the table : *T0N0: 2 LCIS recurred locally after lumpectomy alone. 2 DCIS recurred locally after lumpectomy/RT 5 contralateral tumors (3 DCIS, 2 T1N0) 1 distant recurrence - liver. (alive 4 years later). **T1N0: 9 local recurrences after lumpectomy/RT 7 contralateral tumors. 8 distant recurrences - 3 lung, 2 liver, 3 bone - 4 died ***T2N0: 2 local recurrences after lumpectomy/RT 2 distant recurrences - lung - 1 died ****T1N1: 3 local recurrence after lumpectomy/RT 2 contralateral tumors 2 distant recurrences - 1 bone, 1 supraclav node - 2 died ***** T2–3N1: 1 contralateral tumor 3 distant recurrences - 1 cerv node-2 bone mets - 2 died One hundred and sixteen patients have stopped HRT (47%), 57 because of anxiety about taking HRT (23%), 50 because of breast cancer development (20%), 3 because of the development of non-breast cancers, 2 died of nonmalignant disease, 3 because of HRT-associated symptoms, and 1 because of pulmonary emboli without clinical phlebitis. CHRT, as opposed to ERT, was administered to 50% of all patients and 58% of the 50 who subsequently developed breast cancer on study. Actuarial DFS to 25 years for T1N0 patients was 67% versus 37% (DSS=86%) for comparable T1N0 patients who did not receive HRT. Conclusions: No evidence to date of increased development, recurrence or of breast cancer-related death associated with post diagnosis HRT.

[Table: see text]

No significant financial relationships to disclose.
Frequency, determinants, and temporal trends in lymph node assessment in women with ductal carcinoma in situ
Authors: Griggs J. J. , Sorbero M. E. , Ahrendt G. M. , Stark A. , Dick A. W.
Published: March 2020

11050

Background: This study examined factors associated with lymph node (LN) assessment in women with ductal carcinoma in situ (DCIS) at two sites in the U.S. Methods: Detailed clinical, pathologic, and radiographic information was collected through medical record review for 1090 patients with pure DCIS treated between 1985 and 2000 in Monroe County, New York and the Henry Ford Health System (HFHS), Detroit, Michigan. Sociodemographic, clinical, pathologic, and radiologic factors associated with LN assessment were examined using logistic regression models. Covariates were interacted with a site indicator; models were tested down to include only interactions with treatment and year. Results: 395 (36.2%) women had LN assessment; 43 of these were sentinel node dissections. Of the 438 women who had a mastectomy, 341 (86.3%) had LN assessment compared with 54 (13.7%) of the 598 women who had breast conserving surgery (p = 0.0001). In multivariate logistic regression, factors positively associated with LN assessment were mastectomy (OR, 45.5 95% CI 23.9, 86.5), private insurance (OR 2.3, 95% CI 1.2, 4.4), and high nuclear grade (OR 3.7, 95% CI 1.5, 9.2). Smoking was negatively associated with LN assessment (OR 0.5, 95% CI .3, .9). Age, race, method of detection (palpable mass vs. mammography), histologic subtype, and presence of multifocal disease were not associated with LN assessment. Statistically significant downward trends over time existed and did not differ between the two sites. LN assessment rates differed by treatment by site. Women who had mastectomy at HFHS were more likely to have LN assessment than women who had mastectomy in Monroe County (OR 5.0, 95% CI 1.5, 16.7), but women at HFHS who had autogenous reconstruction following mastectomy were substantially less likely to have LN assessment than their counterparts in Monroe County (OR 0.2, 95% CI .04, .65). Conclusions: The finding that LN assessment rates in women with DCIS vary according to non-clinical factors, such as treatment site and insurance type, suggests uncertainty about the role of LN assessment exists. Local treatment culture and financial incentives may play a role in the variations in LN assessment patterns.

No significant financial relationships to disclose.
Assessment of pathological complete response (pCR) to neoadjuvant dose-dense chemotherapy in HER2+ patients with locally advanced breast cancer (LABC) treated with trastuzumab (T) compared with HER2+ and HER2- patients treated without T
Authors: Sanchez-Muñoz A. , García-Tapiador A. M. , Dueñas-García R. , Jaén-Morago A. , Martínez-Ortega E. , Fernández-Navarro M. , de la Torre-Cabrera C. , Dueñas B. , Morales F. , Sánchez-Rovira P.
Published: March 2020

11057

Purpose: To identify Her2+expression as predictive factor for pCR to T in pts with LABC treated with neoadjuvant chemotherapy. Methods: A total of 127 newly diagnosed stage II-III, including inflammatory tumors, breast cancer pts were reviewed. Median age was 47,7 (r 26,4 - 73,6). Median tumor size was 5 cm (1–10). 57 (44,8%) were T2, 33 (26%) T3 and 37 (29,2%) T4 (25 of them inflammatory). 59 (46,5%) pts were clinically lymph node positive before treatment. 50 pts (39,4%) were hormonal receptor negative, and 38 (30,4%) Her2+. The pts received one of the 2 chemotherapy regimens every 2 weeks with prophylactic growth factors support: A) epirubicin 90 mg/m2-cyclophophamide 600 mg/m2 d1 for 3 cycles, followed by a second sequence with paclitaxel (P) 150 mg/m2- gemcitabine (G) 2500 mg/m2 d1 ± T 2mg/kg/wk according to status Her2 (n= 73); B) adriamicin 40mg/m2 d1 plus P 150mg/m2-G 2000 mg/m2 d2 for 6 cycles (n=54). Subsequently pats underwent surgery and radiotherapy and/or adjuvant hormonal therapy according to institutional practice. Results: 43 (33,9 %) pts achieved a pCR (absence of invasive tumor in the breast). The pts were classified in two groups to analyze the influence of the treatment with T on pCR: (1) Her2+ pats treated with T (20 pts): pCR 50%; (2) The rest of the pts, treated only with chemotherapy (107 pts: 18 Her2+ and 89 Her2- ): pCR 32% (p=0.068). Breast-conserving surgery was performed in 77 pts (60,6%). Conclusions: Both dose dense chemotherapy regimens were highly effective in terms of pCR. Although there were not a significative correlation of Her2+ status and trastuzumab therapy with pCR, probably due to the small number of pts, a favorable tendency was seen in the group of Her2+ tumors treated with T. At the meeting, analysis of the correlation of pCR with progression free survival will be presented.

No significant financial relationships to disclose.
Cardiac safety of pegylated liposomal doxorubicin (PLD) in combination with trastuzumab (T) in patients with metastatic breast cancer (MBC): Results from a multicenter phase II study
Authors: Stickeler E. , Watermann D. O. , Woll J. , Foeldi M. , Gitsch G.
Published: March 2020

1106

Background: Combination therapy of doxorubicin and trastuzumab is highly effective for Her2 positive MBC but characterized by frequent cardiac toxicity (CT). PLD can significantly reduce CT compared to conventional doxorubicin. Patients and Methods: 15 patients were enrolled in a phase II trial to evaluate cardiac safety of T (4 mg/Kg loading dose day 2, followed by weekly 2 mg/Kg) in combination with PLD (40 mg/m2 IV bolus day 1, q 28 d). 75% of pts. presented with more than 1 metastatic site and 40% for second line treatment. PLD was administered for 6 or 9 cycles, respectively, T until disease progression. To assess CT, all pts were evaluated with electrocardiogram (ECG) and echocardiograms (E) for Left Ventricular Ejection Fraction (LVEF) at baseline, every cycle during PLD and T, and every three months during T therapy alone. CT was defined as appearance of signs/ symptoms of congestive heart failure and/or an absolute decrease in LVEF > 10 units (below 50%) or decrease in LVEF > 15 units (above 50%). Results: Four pts. received 6 cycles, 4 pts. received 9 cycles of PLD, 4 pts discontinued treatment due to PD, 3 pts. due to toxicity. After a median follow up time of 15.4 months, 6 pts. (42.9%) demonstrated a clinical benefit and median OS was 16.2 months. Non cardiac side effects were mild with only 3 CTC Grade 3 events of 247 treatment cycles (1.2%). Three pts. developed minor ECG changes without pathological significance and 5 pts. had minor changes in their E with slight diastolic (n=3) or systolic (n=2) dysfunction. During follow-up, 3 pts. were diagnosed with pathological E findings, including 1 slight decrease of LVEF, one diffuse hypokinesia and one strong decrease in LVEF.The median LVEF in the study cohort was 66.1% at baseline, 62.7% after 6 cycles of therapy, 64.4% at the first follow up and did not change significantly until the 5 th examination. Conclusions: This study supports the combination of PLD and H in pts. with HER2 overexpressing metastatic breast cancer as a safe and feasible therapy. Due to the promising clinical response rates in this prognostically unfavorable group, this combination should be evaluated in larger studies as a potential regimen for adjuvant treatment of breast cancer.

No significant financial relationships to disclose.
Is there any difference between microscopic residual disease (pTm) and no invasive disease (pT0) in the breast when there is residual disease in the axilla after primary chemotherapy for breast cancer (BC)? Results of a multicenter study
Authors: Barni S. , Ionta M. T. , Cazzaniga M. E. , Atzori F. , Petrelli F. , Murru M. , Cabiddu M. , Guerzoni D. , Minerba L. , Massidda B.
Published: March 2020

11069

Background: Several studies have demonstrated the importance of achieving pCR both in the breast and axilla, in terms of DFS and OS. We previously demonstrated that no difference exists between microscopic residual (pTm) and no invasive residual (pT0) tumour in the breast in terms of DFS and OS in breast cancer (BC) patients (pts) following primary chemotherapy (CHT). Nevertheless, when pN0 is achieved, we observed a statistical significant advantage for pT0 in comparison to pTm pts (DFS 94.7% vs 80%, p=0.03; OS 100% vs 86%, p=0.08). Aim of the present study was to investigate the clinical significance of pTm in the breast when there is residual tumour in the axilla. Methods: We analysed 48 out of 287 pts with clinical T2–4 BC, who achieved pCR, according to Sataloff’s classification, following different kinds of neoadjuvant CHT. One pt was considered not valuable for clinical outcomes, because lost to follow up. Median age was 47 years (29–68), clinical TN stage was T4 in approximately half of the pts (22/48, 45.8%) and N+ in 11/48 (22.9%). Hormone receptor status was ER- in 20 pts (41.7%) and PR- in 26 (54.2%). All pts received anthracycline-based neoadjuvant CHT, even standard (Q21 days) or intensified (Q14). Median number of administered cycles was 3 (2–6). Median follow up was 89 months (9–189). Results: Thirteen pts (27.6%) had residual disease in the axilla at the end of primary CHT, of whom 6 achieved pT0 and 7 pTm in the breast. Surprisingly, pTm pts had a significant better DFS and OS in comparison to pT0 pts. Results are shown in Table 1 . Conclusions: Our data indicate that the achievement of pT0 in the breast is not of clinical significance when there is residual tumour in the axilla. These results, even if affected by the small number of pts, could be explained by the fact that less aggressive treatments have been delivered to pT0 pts due to the complete clearance of the tumour. [Table: see text]

No significant financial relationships to disclose.
Adjuvant trastuzumab (T) in early stage breast cancer (EBC): Is cardiac dysfunction (CD) clinically significant?
Authors: Dent S. F. , Vandermeer L. A. , Spaans J. N. , Verreault J. L. , Azzi J. S. , Hopkins S. , Verma S.
Published: March 2020

11072

Background: T was funded for women with EBC in Ontario in Aug 05. Clinicians remain concerned about the potential cardiotoxicity of T in women with EBC. The purpose of this retrospective study is to evaluate CD in women with EBC prescribed adjuvant T therapy. Methods: Women with HER2-overexpressing EBC who were initiated on T and chemotherapy (CT) at TOHRCC between Aug 05 and Nov 06 were included in this analysis. A retrospective chart review collected: demographics, CT regimen, T treatment (dose delays, termination of T), CD (defined by the New York Heart Association functional classification, 2002), and management. Results: Outcomes reflect the preliminary results of 108 patients (pts) initiated on adjuvant T therapy. Median age was 52 years (range 30–79). 107 pts (95%) received T and CT; 1 pt received T alone. Pts received an average of 6 cycles of CT (range 1–12), including anthracycline (A; 99%) (A alone 55%; A-taxane 44%) and non-A (1%) regimens. 18 pts (28%) were treated with concurrent T and taxol. Therapy with T has been completed (median 46.7 weeks) in 28 pts (26%) while 72 pts (67%) remain on T. 85% of pts underwent at least 3 MUGA scans during T treatment. CD was observed in 18 pts (17%): congestive heart failure (2 pts), decrease in left ventricular ejection fraction (LVEF) of =10% to less than 55% (14 pts) or decrease in LVEF >20% (2pts). Of 18 pts with CD, 7 underwent a treatment delay (median 8 weeks) 3 permanently stopped T (median 45 weeks) and 8 pts continued T. 31 pts experiencing any decrease in LVEF were managed successfully through: delay, (16 pts), referral to a cardiologist (14 pts) and medical treatment with: ACE-inhibitors (5 pts), beta blockers (1 pt), or combination (2 pts). Discussion: The results of this first analysis indicate that outside of a clinical trial setting, the majority of women receive adjuvant T according to treatment guidelines, do not experience significant CD and are able to complete therapy uninterrupted. The long term consequences of CD in these pts are unknown.

No significant financial relationships to disclose.
Patients’ preferences for adjuvant radiation therapy in early breast cancers
Authors: Pendlebury S. C. , Duric V. , Joseph D. , Rodger A. , Rodger A. , Taylor K. , Hedges R. , Corica T. , Smith R. , Stockler M.
Published: March 2020

11083

Background: Adjuvant radiation therapy (ART) reduces the risk of local recurrence in women with breast cancers. In good prognosis tumours in older women the absolute benefits are small. The aim of this study is to determine the smallest improvement in local recurrence rates that women would consider sufficient to make their adjuvant therapy worthwhile. Methods: 95 women who had completed ART 2–4 years earlier for T1N0M0 breast cancers had their preferences elicited by 1 of 3 interviewers. Women were presented 3 sets of hypothetical scenarios about the risks of recurrence with and without radiation using baseline risks of 5%, 10%,and 20%without ART. The order scenarios were presented was allocated randomly. Results: The women’s median age was 63 years 54% had dependants, and 58% travelled 20km or less to their ART centre. A 1% reduction in risk of local recurrence was judged sufficient to to make ART worthwhile by 77% of the women. More than half the women judged ART worthwhile even if it conferred no benefit. 3–8% of the women judged even the maximum possible benefits insufficient to make ART worthwhile. Women’s preferences were almost identical for all 3 scenarios(Spearman’s rank correlations of 0.89 to 0.94). Preferences were unaffected by the order of scenario presentation, interviewer, participants age, cancer recurrence prior to interview,support during ART, dependants, distance to travel to ART, or time since completing ART. Conclusions: Most women judged small benefits in local recurrence sufficient to make ART worthwhile. Many women judged negligible benefits sufficient suggesting the importance of considerations other than the trade-off between direct benefits and harms.

No significant financial relationships to disclose.
Five-year review of incidence and characteristics of breast cancer referrals to the Mid-Western Cancer Centre, Ireland
Authors: Higgins M. J. , Woulfe B. , Gupta R. K.
Published: March 2020

11084

Background: There are no detailed reports of the epidemiological patterns of Irish breast cancer (BC) patients. The Midwestern cancer centre (MWCC) opened in 2001 and serves an unscreened population of approximately 340,000. We sought to characterise the age, histology, stage and outcome of all newly diagnosed BC patients referred to the MWCC over a 5 year period. Methods: All referrals between January 1 2001 and December 31 2005 were included. We collated information from patient charts, hospital information systems and the Medical Oncology database. Status as of November 1 2006 was established from the database and liaison with local surgical, palliative and primary care services. Results: 505 (504 female, 1 male) referrals of new invasive or non-invasive BC were received in the 5 year period. Of these, 14 were diagnosed with bilateral BC. There were 14 cases of non-invasive BC. Age at diagnosis ranged from 23 to 90 years (y) with an average of 56 and median of 55.3y. Of the 499 breast cancers that were staged at diagnosis, 452 (90.6%) had locoregional disease (AJCC stage IIIC or less) while 47 (9.4%) had distant metastases. Results of pathological analyses of the tumours are shown in table . HER2neu status was not routinely tested in our institution during the review period. Patients were treated according to standard adjuvant or palliative protocols. Follow up data is available for 471 patients with a median length of follow up of 35 months. The Surveillance, Epidemiology and End Results (SEER) program in the USA in a similar time frame (2000–2003) found a median age at diagnosis of BC of 61y in whites with only 5% of these patients having distant spread at time of diagnosis. Conclusions: We present unique and recent epidemiology of BC patients in Ireland’s Midwest. Initial comparison to SEER data suggests that our patients are younger with higher stage disease at diagnosis. [Table: see text]

No significant financial relationships to disclose.