bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and effectiveness of dose dense neoadjuvant chemotherapy in patients with stage II/III breast cancer
Authors: McDaniel S. A. , Krontiras H. , Carpenter J. T. , Nabell L. M. , Bland K. I. , Urist M. M. , Falkson C. I. , Forero A.
Published: March 2020

10622

Background: NSABP B-18 randomized women with operable breast cancer to receive chemotherapy either pre- or postoperatively; OS and DSF rates at 9 years were identical. Importantly, pathologic complete response (pCR) was directly proportional to DFS and OS. Recently, dose dense adjuvant chemotherapy has shown a statistically significant improvement in DFS and OS. However, no data is available for the use of dose dense preoperative chemotherapy at this time. Methods: Women enrolled in the I-SPY correlative trial with newly diagnosed breast cancer, T ≥ 3cm, any N, M0 were evaluated to assess response rates and safety to dose dense neoadjuvant chemotherapy (doxorubicin 60 mg/m2 IV Q2 wks × 4, paclitaxel 175 mg/m2 IV Q2 wks × 4, and cyclophosphamide 600 mg/m2 IV Q2 wks × 4). Results: Since 02/2003, 43 pts have been treated with dose dense neoadjuvant chemotherapy on the I-SPY trial at UAB (mean age 47.9). 47% of the pts were ER+, 37% were PR+ and 5% were Her2+ by FISH. 2 pts dropped out for personal reasons and 9 pts are actively undergoing treatment. Overall, 32 pts received dose dense chemotherapy and proceeded to surgery. Of those, 31 received dose dense sequential ATC and 1 received dose dense concurrent AC followed by T. 34% had a pCR (breast & nodes) while an additional 10% had a pCR in the breast but residual disease in lymph nodes; 41% had a PR; 9% had SD; and 6% had PD. Hematologic toxicity consisted of grade 3 anemia in 2 pts, febrile neutropenia in 2 pts and no grade 4 thrombocytopenia. Non-hematologic grade 3–4 toxicity consisted of mediport-associated thrombosis in 2 pts, hyperglycemia in 2 pts, syncope in 1 pt, neuropathy in 1 pt, and disseminated varicella in 1 pt. Conclusion: Our results show that dose dense neoadjuvant chemotherapy achieves a pCR (breast & nodes) in about 1/3 of patients (34%) with tolerable toxicity.

No significant financial relationships to disclose.
Epidemiologic characteristics of breast cancer (BC) in Asian Indian and Pakistani population living in the US compared to US white population in SEER database from 1988 to 2002
Authors: Abraham J. , Hossain A. , Sehbai A.
Published: March 2020

10657

Background: It is estimated that South East Asian population comprises about 1.5% of the total US population and is rapidly growing. BC is the most common cancer in the US-based Indian/Pakistani female population (38%) as reported in the SEER database. This is the first study reporting different epidemiologic characteristics of BC in this population. Methods: From 1988, Indian and Pakistani population with cancer diagnosis was reported separately. Frequency sessions were performed and epidemiologic parameters for BC were calculated regarding age, marital status, stage, grade, laterality, nodal involvement, menopausal status and hormone receptor status. Results: BC comprises about 19% of all cancers reported in US-based Indian and Pakistani population from SEER database. A total of 804 cases of BC were reported in this group in SEER database from 1988 to 2002. BC is the most common cancer (38%) in US-based Indian and Pakistani female population. In comparison, WHO data from 2002 shows that it is the leading cancer in Pakistani females (34%) and second leading cancer in Indian females (19%). BC is more common in this ethnic group than White female (38% vs 32%, p < 0.01) as reported in SEER database. Table shows the comparative studies of different variables of BC between Indian/Pakistani and US White female reported in SEER database. Conclusion: US-based Indian and Pakistani female population is diagnosed with BC at a younger age than US White population. BC tends to express more receptor positivity. A significant number of females are under 50 at the time of diagnosis. More studies in this subset of patients will help in developing screening and educational intervention in this rapidly growing population.

[Table: see text]

No significant financial relationships to disclose.
Non-pegylated liposomal doxorubicin and docetaxel as front line treatment in HER2-neu negative metastatic breast cancer: Safety and efficacy results
Authors: Cals L. , Nouyrigat P. , Tchiknavorian X. , Dohollou N. , Bertrand F. , Bressac C. , Gomez P. , Facchini T. , Besset M. , Gligorov J.
Published: March 2020

10659

Background: First line docetaxel (D) and doxorubicin (DXR) yield up to 55% response rates in controlled studies, in relapse situation for patients who have received anthracyclin in adjuvant setting, with the risk to run on cardiotoxicity regarding anthracyclin cumulative dose.The objective of the study is to determine efficacy and tolerance of Myocet (M) and D as frontline chemotherapy in her2-neu negative metastatic breast cancer (MBC) patients (pts) who have received anthracyclin in adjuvant setting. Methods: Eligible pts were above 18 years, with MBC relapsing at least 12 month after anthracyclin given in adjuvant setting. WHO = 0–1-2, normal left ejection fraction (LEF), measurable targets, cumulative dose of DXR or epirubicin or mitoxantron previously administred respectively under 300, 600, 75 mg/m2. Ongoing hormonotherapy or radiotherapy had to be stop at least 4 weeks before treatment: M = 60 mg/m2 was given as 90 minutes infusion, followed by D = 75 mg/m2 given as 60 minutes infusion, the both 21 days cycles for 6 cycles. Clinical adverse event review, haematology was performed each cycle, LEF each two cycles, tumor assessment, at day 50 and day 120. Results: Between 04/04 and 05/05: 21 pts with median age 55 (33–72) entered the study. All pts were metastatic (liver 10 pts, bone 9, lung 4, soft tissue 2, skin 2, pleural 1, multiples 6). Premenopausal 6 pts , negative oestrogen receptor: 5 pts. A total of 108 MD infusion has been given, infusions delayed 11, omitted 1, reduced dose 15. Use of neutrophils growth factors 11 pts. No treatment related death has been reported. Grade 3/4 toxicity: febrile neutropenia 6 pts (28%), thrombocytopenia 1, alopecia 21, nausea-vomiting 0, gastritis 1, dental infection 1, one cardiac heart failure grade 3 was observed 6 month after the end of 9 cycles of MD, responsive to angiotensin conversion inhibitor. Efficacy: 10 partials responses, 5 completes responses and 2 progressive disease. RR = 71% Binomial 95% CI (53–85). Conclusions: MD is clinically well tolerated with however 28 % grade 3/4 neutropenia and a large use of neutrophils growth factors, no life threatening aplasia was observed. The high response rate had to be confirm with the safety results at the end of the accrual (50 pts planed).

No significant financial relationships to disclose.
Multicenter phase II study of liposomal doxorubicin (M) and docetaxel (T) as neoadjuvant treatment in patients with stage II - III breast cancer
Authors: Modolell A. , Mayordomo MD J. I. , Garcia-Bueno J. M. , Machengs I. , Alvarez I. , Centelles M. , Palombo H. , Burillo M. , Yubero A. , Murillo L. , Andrés R.
Published: March 2020

10662

Background: T and M is a very active chemotherapy regimen for breast cancer. M has been shown to be as effective as doxorubicin at same doses while reducing the cardiotoxicity and causing less myelosuppression. This study was designed to evaluate clinical and pathological response rate (RR) and toxicity after induction chemotherapy in patient with breast cancer. Methods: Patients with histological confirmation of breast cancer (stage II-III and inflammatory), age > 18 years, left ventricular eject fraction > 45% and adequate bone marrow, renal and hepatic function were included in the study. Prior systemic therapy or radiotherapy and surgery for breast cancer were not allowed. Treatment: T (75 mg/m2) iv and M (75 mg/m2) iv, every 21 days during 4 cycles, followed by surgery. Results: To date 59 patients have been enrolled; 50 were included in this interim analysis, with a median age of 52 years old (28–76), ECOG PS 0, 88.0%; ECOG PS 1, 12.0%; breast location: right, 52.0%; peri-postmenopausal status, 44.9%. Positive hormonal receptor status was 63.3%. Histology was ductal carcinoma in 84.0%. Patients received a total of 188 cycles (median 4, range 2–4). Median relative dose intensity was 99% for T and for M. Efficacy: Nine patients were non-evaluable (7 on treatment, 1 consent withdrawal and 1 lost of follow-up). Of 41 evaluable patients, 5 achieved complete response (CR) (12.2%), 26 partial response (PR)(63.4%), 9 stable disease (SD) (22.0%) and 1 progressive disease (PD) (2.4%), resulting in a clinical response rate (RR) of 75.6% (95% CI: 62.5–88.7%). Surgery was performed in 40 patients: six (15.0%) of them had pathological (p) CR, 25 (62.5%) pPR, 9 (22.5%) pSD resulting in a pathological RR of 77.5% (95% CI: 64.6–90.4%). Median of time to progression and overall survival has not been achieved yet. Hematological toxicities grades III/IV per patient were neutropenia (14%), thrombocytopenia (4%), leukopenia (2%), anemia (2%) and febrile neutropenia (12%). Non-hematological grade III/IV toxicities per patient were asthenia (6%), nausea / vomiting (4%) and infection (4%). Conclusions: T and M every 21 days during 4 cycles as induction chemotherapy in stage II and III breast cancer is an active and well tolerated treatment.

No significant financial relationships to disclose.
Clinical presentation and outcomes of 2,924 early breast cancer patients (br.ca. pts) treated in a single institution in a 10-year period with a long follow up
Authors: Galligioni E. , Triolo R. , Lucenti A. , Ferro A. , Frisinghelli M. , Ambrosini G. , Murgia V. , Micciolo R.
Published: March 2020

10669

Background: A consecutive series of br.ca. pts, treated between Jan 1st 1990 to Dec 31st 1999 in our Department, is the basis of our retrospective study, aimed to create a data base on routinary clinical management of early br.ca. pts, to which compare similar series and literature data. Methods: All Clinical Records were reviewed and computerized. Disease free and overall survival were estimated using the product-limit method of Kaplan and Meier. The log-rank test was used to compare prognosis between different subgroups. Results: Among 2924 consecutive br.ca. pts, 836 were younger than 50 years (med. age 44) and 2088 older (med. age 63). Regional nodes were negative (N−) in 1754, positive (N+) in 1027 and unknown in the remaining pts. So, 2593 pts were stage I-II and 301 stage IIIA-B. Hormonal Receptor status (available on 2560 pts) was positive for Estrogen (ER+) in 2021 pts and for Progesterone (PgR+) in 1649 pts. Moreover, 1571 pts were ER+Pgr+, 539 ER-PgR−, 78 ER-PgR+ and 461 ER+PgR−. HER2 was overexpressed in 262/1426 (18%) pts. Tumor grading (available on 2176 cases) was G1–2 in 1411 and G3–4 in 765 cases. After surgery, 731 pts received adjuvant Tamoxifen, 507 pts CMF ± Antracyclines chemotherapy, 434 pts both chemotherapy and Tamoxifen and 958 pts none. (no therapy data are available for the remaining 334 pts). At a median f.up of 9.8 years, 993/2924 pts (33.9%) have recurred, (med. DFS 137 mos) with a 5, 10 and 15 y probability of recurrence of 26, 44 and 63% respectively. Corresponding figures of recurrence for N− pts were 14, 30 and 50% (med. DFS 168 mos), while for N+ pts were 41, 61 and 77% (med DFS 81 mos). For younger N+ pts treated with chemotherapy, the 5 years probability of recurrence was 34% while it was 24% for older ER+ pts treated with hormonal therapy. So far, 794/2924 (27.5%) pts have died, with a 5, 10 and 15 y probability of death of 13, 27 and 41%. This was 5, 16 and 28% for N- pts and 22, 41 and 56% for N+ pts. For younger N+ pts treated with chemotherapy, the 5 y probability of death was 14%, as it was for older ER+ pts treated with Tamoxifen. Conclusions: Although this data are not yet conclusive, it appears that large part of the clinical improvements reported in clinical trials may be achieved in the routine management of breast cancer pts.

No significant financial relationships to disclose.
Circulating tumour markers and time to progression in the chemotherapy treatment of metastatic breast cancer
Authors: Ruiz-Lopez-tejada M. , Tejedor-Cabrera L. , Iradi-Martinez C.
Published: March 2020

10674

Background: Monitoring the response to the chemotherapy treatment (CT) in metastatic breast cancer (MBC) by circulating tumour markers (CTM) remains under investigation. We have previosly shown that early lack of biological progression of 4 CTM (1 oncofetal: CEA, 2 mucin related: CA 15.3,CA 549 and cytokeratin 18–19: TPA), predicts anatomic disease control - concordance nearly 100% for every CTM- during CT of MBC (E.J.C. Suppl Oct 2005, Vol 3 Abst 415- ECCO 13). The aim is to evaluate whether the biological behaviour predicts time till progression (TTP), as reliable parameter of the quality of response (QR). Methods: In 106 consecutive courses of different schedules of CT given along 3 years in our Hospital to 55 patients with progressive MBC, we conducted a prospective trial analysing these 4 CTM every 3 weeks before CT infusions and performing CTM concentration / time curves. TTP was calculated by Kaplan Meier method -SPSS 11-. Bio kinetic change has been defined as a lineal slope that includes 2 early and consecutive changes of at least 25% of CTM start value. The analysis covered 604 cycles, 405 curves and 2417 marker determinations. Results: Ninety six per cent of the cases have progressed after their CT courses. In CTM expressing diseases, and sometimes after a no more than 3 weeks paradoxical period, three biological patterns could be detected according to directional possibilities: progressive elevation (Bio P), progressive download (Bio R) and stabilization -without bio kinetic change- (Bio S). Table shows the TTP median values in the different group of cases with the same CTM Bio response patterns; Biological Patterns and TTP Kaplan Meier curves will be shown as a Poster at the meeting. Conclusions: In CTM expressing tumours and taking into account simple kinetics criteria, the dynamic analysis of CTM before infusions can early estimates TTP, adding complemmentary information to the disease control prediction in the evaluation of the QR during the CT of MBC.

[Table: see text]

No significant financial relationships to disclose.
Identification of estrogenically synthesized LRP16 as an ERα coactivator and its role in ERα-positive breast cancer
Authors: Han W. , Zhao Y. , Wu Z. , Mu Y. , Yu L. , Meng Y. , Huang K. , Zang L. , Li Q.
Published: March 2020

10676

Background: Aberrant ERα activity is linked to genesis and malignant progression of breast cancer through direct target gene activation or repression. A complex network of coregulatory proteins is largely believed to determine the transcriptional activity of ERα. LRP16 was identified previously to be an estrogen (E2) responsive gene, but its function involving in conferring estrogen signalling pathway is not clear. Methods: Endogenous LRP16 expression in MCF-7 cells was stably suppressed by retrovirus-mediated small interference RNA (siRNA). The effects of LRP16 expression on E2-stimulated growth and invasive ability of MCF-7 cells were determined in vitro and in vivo assays. The effects of LRP16 expression on ERα transactivation were determined by luciferase assays. The interaction of LRP16 and ERα was examined by GST pull-down and coimmunopricipitation (CoIP) assays. Northern blot and Western blot were used to detect the mRNA and protein levels of ER target genes in LRP16-inhibited MCF-7 cells. The LRP16 expression levels in primary breast cancer were detected by Northern blot. Results: Fristly, LRP16 expression was characterized to be dependent on estrogen activities. Then, LRP16 was identified to be an estrogen-independent ERα cofactor in ER-positive breast cancer cells and demonstrate that LRP16 is an essential coactivator to ERα-mediated transactivation in an estrogen-dependent manner. Suppression of LRP16 expression in ER-positive breast cancer cells specifically inhibits the transcription of ER upregulated genes, results in the increase of E-cadherin expression through ER mediation. In vitro and in vivo data demonstrate that suppression of LRP16 inhibits the ability of estrogen-stimulated proliferation and invasiveness of ER-positive breast cancer cells. The pathological and clinical characteristics of human breast cancer includining ER/PR-positiveness, tumor diameter and the involvement of axillary lymphoid nodes were tightly linked with the LRP16 gene expression level. Conclusions: These results establish a mechanistic link between estrogen receptor status, its coactivator LRP16, and progression of ER-positive breast cancers, and may provide a novel antiestrogenic target for the therapy of ER positive breast cancer.

No significant financial relationships to disclose.
Capecitabine (X) plus vinorelbine (N) as second-line therapy in Chinese patients (pts) with metastastic breast cancer (MBC)
Authors: Xu B. , Tian L. , Wu Q. , Zhou M. , Wang H. , Tong Z. , Li H. , Li L. , Hu G. , Shi J.
Published: March 2020

10679

Background: Breast cancer is one of the most common malignancies among Chinese women and the incidence continues to rise, particularly in large cities such as Shanghai. X monotherapy is consistently effective and very well tolerated in pretreated MBC. N is also commonly used in this indication. In several studies, the combination of X + N led to response rates ranging from 43–67% in first-line MBC. As there are few data on this combination in pretreated MBC, we evaluated the efficacy and safety of X + N in Chinese pts with MBC refractory to anthracycline or taxane treatment in a phase II trial. Methods: 77 pts of a planned population of 60 pts were enrolled between Feb 2003 and Nov 2004. All pts had measurable MBC (WHO) recurrent after anthracycline or taxane treatment, Karnofsky PS ≥60, adequate bone marrow, renal and hepatic function. Pts received 3-weekly cycles of oral X 1000mg/m2 bid d1–14 + i.v. N 25mg/m2 d1&8, for at least 2 cycles. Pts with progressive disease went off study while those with complete response (CR), partial response (PR), or stable disease (SD) continued treatment for a maximum of 6 cycles. Results: Baseline characteristics of the 77 pts evaluable to date: median age 51 years (range 29–68); median Karnofsky PS 90 (range 70–100). Previous chemotherapy was: anthracycline (87%), paclitaxel/docetaxel (52%). Principal tumor sites were: lung (40%), liver (39%), lymph nodes (33%), thoracic wall (12%), breast (7%), other (3%). All pts received at least 2 cycles, 20 received 4 cycles and 47 received 6 cycles. The overall response rate was 22%, including 5 CR and 12 PR. At a median follow-up of 6 months (95% CI, 4.2–9.0), the median time to progression (TTP) is 6 months (95% CI, 3.5–9.0). The most common (≥10% pts) treatment-related grade 1/2 adverse events were: HFS (16%), nausea (12%), and SGPT abnormality (10%). Most adverse events improved or resolved after dose adjustment and/or suitable treatments. There were very few grade 3/4 adverse events, the most common being leucopenia (12%). Conclusions: X + N is active in pretreated MBC and its efficacy is confirmed in this study in Chinese pts. The combination is also well tolerated.

No significant financial relationships to disclose.
Phase II feasibility of concurrent docetaxel and post mastectomy radiation after four cycles of AC chemotherapy in patients with high risk operable breast cancer: A trial of the Cancer Research Group Pakistan
Authors: Shah I. H. , Shaharyar A. , Shahid A. , Hafeez M. , Perveen S. , Jameel A. , Shabbir K. , Randhawa I. , Gilani J. A. , Masood A. I. , Javed A. A.
Published: March 2020

10684

Background: Sequential use of docetaxel after four cycles of AC chemotherapy delays the postoperative radiation and can compromise loco-regional control. This delay can be avoided by starting radiotherapy concurrent with the docetaxel. We evaluated the feasibility of concurrent docetaxel and radiation therapy to chest wall and peripheral lymphatics after four cycles of AC chemotherapy. The preliminary results were reported in ASCO 2005 (Abstract 858). Methods: Females between 18–50 years, T2-T3 lesions, four or more positive nodes and hormone receptor negative tumors were eligible. Patients were enrolled after MRM. Four cycles of AC at 60/600 mg/m2 were followed by four cycles of docetaxel at 75mg/m2 every 21-days. Concurrent radiation to chest wall and peripheral lymphatics was started with the third cycle of docetaxel. A dose of 50 Gy in 5 weeks or equivalent was delivered. Successful completion of treatment in 18 out of 20 or 25 out of 30 patients was chosen as an index of feasibility. CTC version 2.0 of NCI and RTOG/EORTC Late Radiation Morbidity Scoring Scheme was used. Results: All the 30 enrolled patients successfully completed the planned treatment. Radiation was completed within 6 months of surgery in 27(90%) of the patients. Febrile neutropenia was seen in 5(16.7%). Grade-3 neutropenia and diarrhea in 8(26.7%) and 6(20%) respectively. Grade-3 dermatitis in the radiated area was seen in 2(6.7%) and grade-2 in 5(16.7%). Late toxicity included grade-2 skin atrophy and telangiectasia in radiated area in 6(20%) each. At a median follow up of 20 months (range 9–25 months) two local recurrences and two systemic relapses have been seen. Conclusion: This treatment schedule is feasible and safe in patients with high-risk operable breast cancer. It allows delivery of post mastectomy radiation within 6 months of surgery in patients undergoing sequential AC-docetaxel chemotherapy.

No significant financial relationships to disclose.
Intrahepatic mitomycin C as treatment of breast cancer hepatic metastasis
Authors: Demey W. , Wildiers H. , Maleux G. , Clement P. , Heye S. , Debruyne P. , Van Oosterom A. , Paridaens R.
Published: March 2020

10690

Background: Because of increasing survival due to improving systemic treatment, liver metastasis represents a major and increasing cause of death in women with metastatic breast cancer. Regional treatment is an attractive option in the treatment of liver metastases. We reviewed the tolerability and efficacy of intrahepatic administration of mitomycin C (MMC) performed in our institution. Patients with only or predominant liver metastasis were eligible, independent of previous chemotherapy for metastatic breast cancer. Methods: In a unicentric protocol we reviewed retrospectively all patients (n = 11) who received intrahepatic MMC for liver metastasis of breast cancer between January 2000 and July 2005 in the University Hospital Leuven. MMC was administered as a bolus of 6 mg in 50 ml saline directly into the right and left hepatic arteries by transcatheter technique. The procedure was performed by an interventional radiologist. Patients were hospitalised for 24 hours. In patients with severe liver function disturbances or more than six administrations of MMC a dose reduction was applied. Results: All treated patients were reviewed. The median age was 52 years (range, 36–61). Most patients were heavily pre-treated with a median of 4 systemic chemotherapy regimens (range, 1–5). Treatment was well tolerated, no grade 3 or 4 adverse events were reported. Only one patient had persistent thrombocytopenia for which interruption of treatment was required. One patient had fatigue. There were no procedure-related complications. Six patients received only 1 or 2 administrations because of rapid disease progression within the first two months. Among the remainders, 4 patients had 6 and 1 had 11administrations. When evaluatde by RECIST criteria one patient had a complete remisson, two patients had a partial remission and 2 patients remained stable for at least 6 months. Conclusions: In this retrospective analysis intrahepatic administration of MMC was well tolerated and provided clincal benefit (respons or at least disease stabilization for 6 months) in 45% of heavily pre-treated patients. This treatment represents a valid therapeutic option for patients with predominant liver metastases of breast cancer after failure of standard systemic treatment.

No significant financial relationships to disclose.
Phase I-II study of IV vinorelbine (VRL) and oxaliplatin (OXP) every two weeks (q2w) in metastatic breast cancer (MBC): Results of the phase I trial
Authors: Rodriguez-Lescure A. , Llombart A. , Colomer R. , Gutierrez G. , Gayo J. , Tusquets I.
Published: March 2020

10691

Background: The combination of VRL and OXP was shown to be effective for the treatment of NSCLC. We designed a scheme for first line MBC consisting of administering IV VRL and OXP q2w to explore potential synergistic effects, to determine the maximal tolerated dose (MTD), recommended doses (RDs) and safety of the combination. Methods: Twelve patients (pts) entered the study. Four dose levels were established: A) VRL 25 mg/m2 with OXP 80 mg/m2, B) 25/90, C) 25/100 and D) 30/90, both drugs q2w. Patients/cycles analyzed were: A) 3/15, B) 3/21, C) 3/15, D) 3/19. Results: Median age 58 y (range; 39–78), 10 pts (83%) received prior (neo)adjuvant CT. No dose limiting toxicities were found at any of the dose levels. RD was established at IV VRL 30 mg/m2 and OXP 90 mg/m2/d both administered every 2 weeks. A total of 71 cycles were analyzed. Grade 3 neutropenia occurred in 4 pts (44%) and 13% of cycles, grade 4 in 1 pt (11%) and 1% of cycles. No complications were observed. No grade 4 non-haematological toxicity was seen. Grade 3 neurotoxicity occurred in 1 pt and 2 cycles, grade 3 fatigue occurred in 1 pt and 3 cycles. 2 partial responses were observed among the 6 evaluable patients for response. Conclusions: The combination of VRL and OXP is safe in the palliative setting of MBC. Phase II study explores the efficacy and safety of the combination of VRL 30 mg/m2 and OXP 90 mg/m2 q2w. Recruitment is ongoing.

No significant financial relationships to disclose.
Relationship between tumor characteristics and HER2/neu overexpression with response and outcome in locally advanced breast cancer (LABC) patients (pts) treated with neoadjuvant anthracycline-based chemotherapy (CHT)
Authors: Fernandez Sagarra A. J. , Alvarenga C. , Alvarenga M. , Kraft M. L. , Teixeira L. C.
Published: March 2020

10698

Objectives: To retrospectively evaluate the relationship between HER2/neu status, pts’ characteristics, prognostic factors and clinical outcome in LABC women treated with neoadjuvant anthracycline-based CHT. Patients and Methods: 118 pts. with stage IIIA-B LABC, excluding inflammatory cancer, were included. HER2 overexpression was evaluated by immunohistochemistry (IHC), only IHC 3+ were defined as positive. The disease-free survival (DFS) was calculated according to Kaplan-Meier method. Fisher test, hazard ratios with 95% interval confidence, and Cox or Wilcoxon models were used. Kruskall-Wallis was used for comparison between medians. Results: Median age was 49 y (range: 31–69); 66 were pre-menopausal, 43 were stage IIIA and 77 IIIB; 59 pts. were N2. Primary tumor average size was 70 mm; 44 tumors were ER+, 43 PR+, 26 (22%) HER 3+, 104 histological grade III, 57 nuclear grade III. Seventy-four pts. (62.7%) achieved objective responses, with 7 complete clinical remissions. There was 1 progressive disease and only 3 pts. (2.5%) didn’t undertake mastectomy. After surgery, four pts. (3.5%) were evaluated as pathological complete remission, 6 (5.2%) with microscopic residual disease and 105 with macroscopic residual tumor. The median DFS was 19 months for the whole group and 39,6 and 31,6 for those achieving complete pathological remission and microscopic residual disease, respectively. There was no association between HER2/neu overexpression and pts’ characteristics, tumor prognostic factors nor with clinical or pathological responses. Negative PR, high tumor nuclear grade, clinical stage IIIA and complete clinical response were predictive factors for pathological response. In multivariate analysis, only pathological lymph node status was prognostic factor for DFS. Conclusions: There was no significant association between HER2 overexpression, tumor prognostic factors and clinical or pathological response to neoadjuvant CHT. Negative PR, high nuclear tumor grade, clinical stage IIIA and clinical complete response were associated to complete pathological response. Lymph node status was a strong prognostic factor for DFS.

No significant financial relationships to disclose.
Addition of weekly paclitaxel (P) after dose intensified epirubicin/cyclophosphamide (EC) (NECTA-protocol) as primary systemic chemotherapy (PST) in locally advanced breast cancer (LABC) improves pathologic response rate (pCR) in comparison to peoperative dose intensified EC
Authors: Lex B. , Popovic M. , Russu V. , Gilster T. , Volkholz H. , Tulusan A. H.
Published: March 2020

10712

Background: Green M et al. (Proc Am Soc Clin Oncol 2002, abstract 135) demonstrated an improvement of pCR up to 28,8% by changing the preoperative application of 3 weekly P 225 mg/m2 (q21) to weekly P 80 mg or 150mg/m2 (q7) completed by 4 cycles FAC. Our study-group observed a pCR of 6% after 3 preoperative cycles of dose-intensified EC (120 mg/600 mg/m2 q14 or q21) in LABC. Dose-density (q14) did not improve pCR (Euler U et al. Proc Am Soc Clin Oncol 2002, abstract 126). As a consequence we studied the preoperative effect of 12 cycles P 80 mg/m2 (q7) after 3 cycles EC (120 mg/600 mg/m2 q21) . Methods: Between 2002 and 2005 61 patients (pts) with LABC (T2–4/N0–2/M0) were operated after PST with the NECTA-protocol. Irradiation after breast conserving therapy (BCT) was obligate. Immunohistochemical analysis were performed in tumor tissues from core biopsy before PST and from surgery. Results: The medium age was 49,2 yrs, 29,2% had negative ER-status, 48,1% negative PR-status and 22% HER2 overexpression. 76,2% had a cT2-tumor, 18,6% a cT3-tumor and 5,1% a cT4-tumor, 48,3% clinically showed positive lymph nodes. The medium follow up was 27 months (2–41 months). The clinical and pathological response rate was 94,8%. pCR was diagnosed in 8,6%. BCT was feasible in 94,8%. The documented recurrence rate was 14,7% (9 pts: 4 with local relapse, 3 with metastases and 2 with simultaneous local and distant recurrence), 8 pts with recurrence had a cT2-tumor. In the meantime 3 pts died. Conclusions: The additional treatment with weekly paclitaxel after EC induced a high rate of clinical and pathological response. The rate of conservative surgery was very high (94,8%). In the retrospective analysis NECTA-regime improved pCR. In comparison to other taxane-based PST-protocols pCR-rate (8,6%) was low. A phase III study will compare the NECTA-regime with the classical EC-regime in PST.

No significant financial relationships to disclose.
Safety and efficacy trial of preoperative sequential chemo-radiation therapy for the surgery sparing treatment (SST) in early breast cancer (EBC): Japan Clinical Oncology Group trial (JCOG0306)
Authors: Mukai H. , Watanabe T. , Mitsumori M. , Tsuda H. , Nakamura S. , Masuda N. , Asaga T. , Yamamoto N. , Kaba H. , Aogi K.
Published: March 2020

10717

Background: The combination of preoperative anthracycline-containing regimen and taxane can obtain a pathological complete response (pCR) rate of around 30% for patients (pts) with EBC. To pursue higher pCR rate with maintaining good systemic control is necessary to put the SST practical in the future. The objective of this trial was to determine whether the addition of radiation therapy (RT) to chemotherapy (CT) could surpass the pCR rate of 50% in pts with EBC. Methods: We conducted a safety and efficacy trial of CT (4 courses of doxorubicin and cyclophosphmide (60/600 mg/m2) followed by 12 courses of weekly paclitaxel (80 mg/m2) and RT (whole breast 45Gy + boost 10Gy) sequentially as a primary therapy in pts with stage I-IIIA (5.0 cm ≥ tumor size ≥ 2.0 cm) BC. All pts received mastectomy or lumpectomy 12–16 weeks after completion of RT to maximize the effect of RT. pCR was assessed by the central pathological review board according to the pCR classification adopted by the National Surgical Adjuvant Breast and Bowel Project (NSABP). The study was designed to enroll 104 eligible pts with threshold pCR 35%, expected pCR 50%, alpha 0.05, beta 0.1, and additionally to have the width of 95% confidence interval (CI) within ±10% for sufficient precision of pCR. Results: Between June 2004 and April 2005, 108 pts were enrolled in this trial. Median age was 50 years (range 23–69). 1 pt had T1, 95 T2, and 3 T3 tumors (2 pts’ data are missing and 7 pts’ data have not been collected). 58% (59/101) were ER+, 49% (49/101) were PgR+ and 31% (31/101) had HER2 overexpression. Based on the planned interim analysis, the Data Monitoring Committee recommended to terminate the trial for insufficient pCR rate of the first 7 eligible patients (0% (0/7), 95% CI: 0–41.0%). Toxicities were within expected range. Conclusions: Preoperative sequential chemo (AC followed by paclitaxel) -radiation therapy is not considered to be promising for accomplishing enough pCR rate.

No significant financial relationships to disclose.
Trends in systemic management (SM) for the treatment of locally advanced breast cancer: Data from a regional cancer centre
Authors: Dent S. F. , Verma S. , Azzi J. , Vandermeer L. , Spaans J.
Published: March 2020

10728

Background: Locally advanced breast cancer (LABC) accounts for less than 5% of women diagnosed with breast cancer in North America each year. The scarcity of clinical trials addressing the SM of these women continues to represent a challenge for clinicians. Methods: A retrospective database was developed using the American Joint Committee on Cancer (AJCC) 2002 staging classification for all women who presented to TOHRCC with LABC between Jan 1/02-April 1/05. Information was obtained from clinic charts and patient self-reported questionnaires. Results: Outcomes reflect the SM of the first 50 women entered into our database. Median age at presentation was 57 years (range 28–88); 62% were post-menopausal; and hormonal status was 52% estrogen receptor (ER) positive and 54% progesterone receptor (PR) positive. Surgery was performed prior to chemotherapy in 50% of patients (pts).The majority (90%) of pts received SM as follows: 38% anthracyclines (A) alone (52% epirubicin, 26% adriamycin, 2% both); 7% taxanes (T) alone (33% paclitaxel, 66% docetaxel), 53% received both T and A regimens, and 2% received other types of chemotherapy (gemcitabine,vinorelbine,capecitabine). The addition of trastuzumab to the SM of HER2-positive pts has also been observed. Hormone therapy was given to 22 pts (44%) of whom 82% were ER or PR-positive: tamoxifen (27%); aromatase inhibitors (AIs; 50%); both tamoxifen and AIs (23%). Pts were treated with AIs as follows: anastrozole (73%); fulvestrant (9%), and atemestane (9%). In pts with measurable disease receiving neoadjuvant SM; 7(35%) had a complete clinical response and 13 (65%) had a partial response; mean tumour size decreased from 7.5 cm (range 2–22) to 2.8 cm (range 0–8). Pathological complete response rates and improved survival rates have been observed and will be reported in detail. Conclusions: These results represent our first analysis of treatment outcomes in women with LABC using the new AJCC system. This database highlights the increased utilization of T and AIs in the SM of these pts, which seems to translate into the increasingly observed improvements in overall survival. Microarray studies to further explore predictability of treatment outcomes are planned.

No significant financial relationships to disclose.
Phase II study of gemcitabine (Gem) + docetaxel (D) in combination with trastuzumab (T) in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC)
Authors: Fescina D. R. , Gradishar W. , Orlando M. , Rubinsak J. , Haney L. , Wang Y.
Published: March 2020

10730

Background: Addition of T to chemotherapy (chemo) is assoc. with improved overall survival (OS) in pts with HER2+ tumors. Combination chemo has shown improvements in PFS and OS over single agent in recent phase III studies. Pre-clinical models suggest that the combination of G and D appears to be synergistic and that either agent is also synergistic with T. Objectives: This multi-institutional study was designed to determine overall RR (primary endpoint), TTP, OS and the toxicity profile of the combination of G + D + T as first-line therapy for MBC pts. Design: Pts with measurable HER2-overexpressing (FISH+) MBC, no prior chemo in the metastatic setting, adequate end-organ function and PS 0–2, received Gem 1,000 mg/m2 over 30 min on days 1 and 8 + D 75 mg/m2 day 1 and T on day 1 (8 mg/kg over 90 min on cycle 1, then 6 mg/kg over 30 min on subsequent cycles) of a 21-day cycle, until progressive disease or undue toxicity. Results: 8 pts have been enrolled over a period of 16 months. Median age: 53 years (range 40–74); ER status ±: 5/3 pts; ECOG PS 0 = 3 pts, 1 = 4 pts, 2 = 1 pt; Prior adjuvant therapy: Chemo ± Hormonal 3, Hormonal only 3, T 1. Sites of Disease: All pts had visceral involvement (Lung 4, Liver 5) and 5 pts ≥ 2 sites of metastatic disease. Total number of cycles administered was 52; median per pt. 7 (range 4–10). Median delivered dose intensity for G, D and T was 91%, 92% and 100% respectively. Toxicity was generally manageable. One pt discontinued therapy due to adverse events (grade 3 pneumonitis). Grade 3/4 neutropenia occurred in 27% and 10% of cycles; no grade 3/4 anemia or thrombocytopenia were recorded; Non-Heme toxicities of grade 2/3, included with dyspnea (0/2 pts), emesis (2/1), fatigue (4/1), diarrhea (1/1), dehydration (0/1), constipation (1/0). Complete alopecia was observed in 2 pts. No symptomatic cardiac toxicity was recorded. Best Overall RR assessment (N = 8): CR 3, PR 4, SD 1, PD 0, for an ORR of 7 out of 8 pts or 88% (95% CI: 47%–100%). Only 3 pts have progressed, and no pt has died. Progression-free survival at 1 year is 58%. Conclusion: According to this limited experience, the combination of G + D + T in front-line MBC is well tolerated and active. Study was discontinued due to slow accrual as of Feb 2004. Supported by Eli Lilly & Company.

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Aromatase inhibitors (AIs) with or without GnRH agonist as first-line hormone therapy in pre- and post-menopausal Korean women with metastatic breast cancer (MBC): Clinical outcomes in correlation with tumor ER/PR/HER2 status
Authors: Ro J. , Lee K. S. , Nam B. H. , Lim H. S. , Kwon Y. , Kong S. Y. , Seo J. A. , Lee E. S.
Published: March 2020

10732

Background: Clinical outcomes of patients (pts) with MBC by AIs in comprehensive relationship with ER/PR/HER2 status have been scant that the study was performed to analyze their predictive values singly and in combination. Methods: 111 pts who took letrozole or anastrozole as first-line hormonal therapy for MBC were identified from the database at NCC Hospital between Nov. 2001 and Aug. 2005. Pts on AIs concomitantly with or immediately followed by chemotherapy were excluded. AIs/GnRH agonists were used when hormonal levels were not postmenopausal. ER/PR were scored strong, intermediate or weak. HER2+ was IHC 3+ or FISH+. HER2− was IHC 0, 1+ or 2+/FISH−. Clinical benefit (CB) included CR/PR/improving or SD ≥6 months. Results: Median age was 54 years (range, 29–78). Overall 66% achieved CB (CR/PR 18%, improving 26%, and SD ≥ 6mo 22%) with median TTP, 9 mo (range, 1–50, 95% CI, 7–11), and median survival, 41 mo (range, 2–50). Age, AIs with (20) vs. without (91) GnRH agonist, DFI ≤ vs. > 24 mo, adjuvant tamoxifen, or prior metastatic chemotherapy did not affect clinical outcomes. Disease sites (%) were bone (64), LN (52), lung/pleura (41), liver (25), breast (20) and skin (7). Bone only disease had longer TTP (p = 0.004), while liver involvement was associated with short TTP (p = 0.0001)/OS (p = 0.007). ER was 56% strong +, 21% intermediate +, 15% weak +, 5% - and 3% unknown, PR: 24% strong +, 23% intermediate +, 24% weak +, 23% -, and 5% unknown, and HER2: 23% +, 67% -, and 10% unknown. Staining intensity did not affect CB in ER+ tumors. More CB (p = 0.002)/longer TTP (p = 0.003) with strong/intermediate PR+ tumors vs. weak PR+/PR− tumors, and more CB with ER+/PR+ tumors vs. ER+/PR− tumors (P = 0.016) were observed. More CB with HER2− tumors vs. HER2+ tumors (p = 0.001), and with PR+/HER2− tumors vs. the rest (PR−/HER−, PR+/HER+, PR−/HER+) (p = 0.0007) were seen. HER2 positivity was associated with less CB (p = 0.0004)/shorter TTP (p = 0.0157) in ER+/PR+ tumors vs. no influence on CB (p = 0.245)/TTP (p = 0.52) in ER+/PR− tumors. Conclusions: AIs with or without GnRH agonist are effective therapy for pts with MBC, specifically with ER+/PR+/HER2− tumors regardless of ages.

No significant financial relationships to disclose.
Age is not a prognostic factor in Korean women with breast cancer treated with breast conservative surgery and radiotherapy
Authors: Choi D. , Kim E. , Kim Y. , Lee M. , Park H.
Published: March 2020

10740

Background: The median age of the breast cancer at diagnosis in Korean women is 45 years and a quarter of the patients are at age 40 or younger. The purpose of this study was to analyze the prognostic factors including age for patients treated with breast conserving surgery and radiotherapy. Methods: Two hundred and eleven breast cancer patients were treated with breast conserving therapy at Soonchunhyang University Hospital, Seoul, Korea, between May 1991 and May 2003. The radiation dose to the whole breast was 50.4 Gy over 5 weeks and boost doses of 10–14 Gy administered to the tumor bed in the majority of the patients (180/211). Nodal radiotherapy was delivered in patients with 4 or more node metastasis. Adjuvant chemotherapy was performed in most of the patients with node metastasis or tumors larger than 1cm, or younger patients. One hundred and thirty four patients received CMF regimen, 14 patients treated with CEF regimen. The median and minimum follow-up periods were 58 and 30 months respectively. Results: The average age at the time of operation was 41.9 years (median 42 years, range 23–67 years), and the mean tumor size was 2.03 cm (median 1.80 cm). One hundred and forty seven patients (69.7%) had pathologically node negative disease and fifteen patients had 4 or more lymph node metastasis. Local, regional relapse and distant metastasis occurred in 7, 3 and 10 patients respectively. The 5 year disease free, loco-regional relapse free and overall survival rate were 89.5%, 93.4%, 95.6%, respectively. Three patients among the 31 patients who received 50.4Gy or incomplete radiotherapy to the breast experienced loco-regional relapse. Age (40 years or less versus more than 40 years old) was not a prognostic factor in univariate analysis. T stage (p = 0.027), lymph node metastasis (p < 0.01) were significant factors for recurrences. By multivariate analysis, only lymph node status was a significant prognostic factor for treatment related failure. Conclusions: A breast conserving procedure is effective for patients with early stage breast cancer regardless of age in Korean women. Axillary lymph node status was the most important independent predictor for a recurrence, and more efficient treatment is required for these patients with lymph node metastasis.

No significant financial relationships to disclose.
Clinical experience using fulvestrant in hormone responsive metastatic breast cancer
Authors: Bauerschlag D. O. , Schem C. , Jonat W. , Maass N.
Published: March 2020

10749

Background: We report our clinical experience using the steroid estrogen receptor antagonist Fulvestrant to treat postmenopausal women with hormone sensitive metastasized breast cancer. We discuss the position of Fulvestrant in the endocrine treatment cascade, taking into account the new application guidelines for aromatase inhibitors. Methods: Data from 16 female patients and one male patient treated with Fulvestrant were analyzed. We describe the time point in the treatment cascade when Fulvestrant was administered and the resulting time to progression (TTP). The reviewed cohort was heterogeneous regarding the initial tumor size, the therapy and the progression of the tumor, respectively. The patients were 54 years of age at the time of diagnosis. The estrogen receptor was positive in all cases. Results: Fulvestrant was usually given as the last step in the endocrine treatment cascade (n = 14). The mean TTP was 5.7 months (n = 13). 3 patients are still under successful treatment with Fulvestrant. No common side effects as usually caused by endocrine therapies with Tamoxifen and aromatase inhibitors were documented. Conclusions: The specific estrogen receptor down-regulator Fulvestrant is a valid and well tolerated endocrine treatment option in heavily pre-treated and metastasized breast cancer patients (TTP 5.7 month). Also in the clinical situation of Tamoxifen resistant tumors, Patients could benefit from Fulvestrant. 3rd generation aromatase inhibitors are now used for the first-line treatment of breast cancer in postmenopausal women. Shifting the sequential endocrine therapy cascade might need a new positioning of Fulvestrant.

No significant financial relationships to disclose.
Three years follow up in patients with stage III breast cancer: Single institution experience
Authors: Stojkovski I. , Kraleva S. , Smickoska S. , Crvenkova S.
Published: March 2020

10752

Background: Purpose of this study is to estimate impact of different prognostic factors and treatment procedures on overall survival of patients with stage III breast cancer, treated at the Institute of Radiotherapy and Oncology (IRO) in Skopje, Macedonia. Methods: Retrospective analysis of patient records of forty four patients with stage III breast was performed. Before admitting at IRO, each patient undergoes surgical treatment, which comprises of radical mastectomy with ipsilateral axillary dissection. Patients were classified according to TNM system of AJCC. All patients were divided in groups according to primary tumor size (unknown, less than 5 cm and more than 5 cm), positive lymph nodes (4–9 positive lymph nodes or more than 9 positive lymph nodes), adjuvant chemotherapy (CMF like, antracyclines based and taxanes based) and elective radiation of thoracic wall and regional lymph nodes (with or without radiation). Results: Statistical analysis of data was performed with Kaplan Meier estimation and log-rank test. In our series only tumor size has significant impact on overall survival of patient (p = 0.0134). Nodal status, type of adjuvant chemotherapy used and radiation has no significant impact on overall survival. Conclusions: Further analysis and longer follow up of this subgroup of patients is necessary to estimate value of different prognostic factors and treatment modalities.

No significant financial relationships to disclose.