bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and pathological correlations in male breast cancer (MBC): Intratumoral aromatase expression (ITA) via tissue microarray (TMA)
Authors: Gray S. , Dakin-Hache K. A. , Barnes P. J. , Dewar R. , Younis T. , Rayson D.
Published: March 2020

10553

Background: Most cases of MBC are hormone-receptor (HR) positive and there is anecdotal evidence of disease response to aromatase inhibitors in the metastatic setting. Study objectives were to (i) assess clinical-pathologic characteristics in a cohort of MBC, (ii) evaluate intratumoral aromatase expression and (iii) assess its’ prognostic impact. Methods: A retrospective chart review was conducted for all cases of MBC seen at the Nova Scotia Cancer Centre between 1985–2005. Data abstracted included disease stage, tumor grade, HR status (ER/PR), HER2-neu and ITA expression as well as dates of disease recurrence and death. Tumor blocks were incorporated into 3 TMA’s with control specimens (gynecomastia, benign breast tissue, liver). Four 1.0 mm cores were taken of each tumor. Immunohistochemistry (IHC) was performed with the following antibodies; 6F11 ER primary Ab (Ventana, USA), 1A6 PR primary Ab (Ventana, USA), TAB250 monoclonal mouse anti-HER2 (Zymed, USA), DAKO 0185 rabbit anti-human c-erbB2 (DAKO, Canada), mouse anti-human p450 aromatase Ab (Cedarlane, Canada). ITA staining intensity and distribution was compared to benign hepatic tissue and if > or = to liver was called ’strong’ while < liver was called ’weak’. The log-rank test was used for survival comparisons. Kaplan-Meyer curves were used to estimate 5year disease-free (DFS) and overall (OS) survival probabilities. Results: 54 cases were identified with median age at diagnosis of 64 (31–85 yrs). Median tumor size was 2.6 cms (0.9–8cms) and 22 (41%) had nodal metastases. 45 cases had tissue available for IHC. Of these, 40 (89%) were ER and 33 (73%) were PR positive. HER2-neu was overexpressed in 4/42 (9.5%) and 12/45 (27%) had strong ITA expression. 5 yr DFS was 71% and OS was 64%. In univariate analysis strong (vs weak) ITA expression was associated with improved 5 yr OS (92% vs 49%, p = 0.038) but not DFS (82% vs 76%, p = 0.44) rates. Conclusion: The suggestion of improved OS but not DFS for those tumors with strong ITA expression may imply that these were more responsive to hormonal therapy in the metastatic setting or had a more indolent pace of progression. It is suggested that further investigation of ITA and response to hormonal therapy in MBC is warranted.

No significant financial relationships to disclose.
A prospective survey evaluating the use of soy products in breast cancer
Authors: Walker S. , Franciose J. , Vashi P. G. , Lammersfeld C. , Grutsch J. F. , Lis C. G. , Gupta D. , Williams S.
Published: March 2020

10562

Background: Many studies have evaluated the potential role of soy in the prevention of breast cancer. A number of components in soy appear to have anticancer properties, including isoflavones, genistein and daidzein. The use of soy by women with breast cancer is now being questioned because of the estrogen-like effects of isoflavones and possible interactions with tamoxifen. Clinicians providing nutrition counseling to these women are concerned because the availability of soy foods has increased dramatically in the past few years. The goal of this study was to quantify the intake of isoflavones in women with breast cancer to determine if their intake is of clinical significance. Methods: We evaluated a consecutive case series of 100 women with breast cancer treated at Cancer Treatment Centers of America between 09/03 and 02/04. After obtaining informed consent, each patient was asked to complete a soy food frequency questionnaire (FFQ) that was scored by Fred Hutchinson Cancer Research Center, the institute that developed and validated FFQ. Results: Mean age was 50.5 years (std. dev. = 9.4; range 31–70) and mean BMI was 27.3kg/m2 (std. dev. = 6.75; range 17–59). Table 1 shows detailed characteristics of our patients. Genistein and Daidzein consumption was limited to 65 patients with a mean intake of 81.5 mg/week (std. dev. = 153; range 0.02–682) and 52.9 mg/week (std. dev. = 98.8; range 0.02–482) respectively. Soy foods with highest reported consumption were soy sauce (37%), soy milk (23%), soy bars (18%), roasted soy nuts (13%) and tofu (13%). Conclusions: Our study suggests that the isoflavone intake of breast cancer patients at our hospital was quite variable. Thirty-five patients reported no soy intake. The mean daily intake translates into 11.6 mg genistein and 7.4 mg daidzein, which is equivalent of less than ¼ cup of tofu per day. This amount is slightly higher than what has been previously reported in non-Asian American women.

[Table: see text]

No significant financial relationships to disclose.
Differential gene profiling of malignant cells and fibroblasts from the primary and metastatic sites from breast cancer patients upon stroma-epithelial cell interaction
Authors: Koike Folgueira M. A. , Honda S. T. , Benvenuti T. T. , Rozenchan P. B. , Santos R. P. , Brentani H. , Carraro D. M. , Katayama M. H. , Lyra E. C. , Brentani M. M.
Published: March 2020

10570

Background: In breast cancer (BC), stromal-epithelial cell interactions may influence tumor development in the primary tumor (PT) and metastatic sites, which may be reflected by a differential phenotype of malignant cells and fibroblasts (Fb). Methods: To investigate the role of stromal cell interactions in tumor development in the primary site and in lymph nodes (LN), primary culture of Fb obtained from breast tissue: PT (n = 4) or peritumoral (n = 4); and LN: involved (iLN, n = 3) or uninvolved (n = 3) from BC patients, were established. Fb and normal (MCF10A) or malignant breast cells (MDA-MB231) were cultured isolated or co-cultured separated by a porous membrane, for diffusion of soluble factors. Gene profile of epithelial cells or Fb were analyzed separately in cDNA microarray slides. Gene expression of co-cultured cells were compared to that of cells cultured alone and differentially expressed genes were those satisfying a FDR <0.01 and > 2 fold variation. Genes exclusively regulated during malignant conditions (MDA-MB231 cells co-cultured with Fb from PT or iLN) were selected on Venn diagrams. Results: Gene profile from MDA-MB231 cells may be influenced by Fb from the PT as 74 genes were differentially expressed upon co-culture as compared to MDA-MB231 cells maintained alone, including genes involved in DNA metabolism and regulation of transcription. Ninety nine genes were modulated in MDA-MB231 cells co-cultured with Fb from iLN, as those involved in RNA metabolism, phosphate metabolism and protein catabolism. Only 2 genes were commonly down-regulated in malignant cells upon co-culture with Fb from PT and iLN, KATNB1 and ZNF19, which modulation seem important for tumor development in both sites. In addition, malignant cells differentially affect gene expression of Fb from PT or iLN. Conclusions: Upon co-culture between Fb obtained from PT and iLN with malignant cells, a reciprocal regulation of a differential group of genes was observed, which may be important for tumor development in these different sites. This model may allow identification of candidate genes involved in stromal-cell interactions during tumor development in PT or LN. Supported by FAPESP and CNPQ.

No significant financial relationships to disclose.
Prognostic facctor for early versus late relapse in hormonodependant non metastatic breast cancers treated by tamoxifen: PROFARE study results from GETNA group
Authors: Azria D. , Tubiana-Hulin M. , Spielmann M. , Coudert B. , Monnier A. , Serin D. , Altweeg T. , Namer M. , Gligorov J.
Published: March 2020

10585

Background: The purpose of this study was to identify potential prognostic factors of early relapse among postmenopausal women with ER+ breast cancer treated at least by adjuvant tamoxifen therapy. Methods: This was a multi-center, retrospective study. Data was collected from 1588 subjects on demographic and subject characteristics and the subjects’ course of the disease using information from patient files. It was planned to have data to cover a follow-up period of ten years. Frequency distributions of the pre-specified potential prognostic factors were presented for subjects with relapse or death (RoD) below 3 years (early), RoD after at least 3 years (late) and without RoD recorded. Results: There were 1550 subjects included in the analysis population. The median age was 60 years [52–67]. There were 633 patients (40.8%) with an event for RoD. Median relapse-free survival time (RFS) was 165 months (no confidence interval calculation possible due to low event rate) and lower quartile relapse-free survival time was 68 months [95% CI, 59–76]. Concerning RFS 212 (13.7%) subjects had an early relapse and 421 (31.5%) had a late relapse. Out of 1550 subjects analyzed for overall survival, there were 344 (22.2%) with an event. Median survival time was not reached; lower quartile survival time was 143 months [131–176 months]. The Cox regression for RFS showed that prognostic factors for RFS overall and for early RFS seems to have similar patterns. Prognostic factors for late RFS differed from those for RFS overall and early RFS. The Cox regression for overall survival showed similar results. SBR grade 1 or 2 vs. 3 (p < 0.0001), <4 vs. ≥4 lymph nodes involved (p < 0.0001), and tumor size pT0–1 vs pT2–4 (p = 0.0001) are selected in both models as prognostic factors. These factors are also of prognostic value for RFS. Conclusions: Women with hormonodependant breast cancer who are at high risk of early relapse while on tamoxifen can potentially be identified. These data could maybe be of importance concerning the choice of the upfront hormonal regimen in menopaused women treated for hormonodependant breast cancer.

No significant financial relationships to disclose.
Oral vinorelbine in combination with capecitabine in advanced breast cancer
Authors: Gil-Delgado M. , Boostan H. , Garcia-Giralt E. , Auclair G. , Biville F. , Khayat D.
Published: March 2020

10586

Background: the availability of chemotherapeutic drugs given by oral route represents a step forward in the management of cancer patients (pts). Vinorelbine and capecitabine have demonstrated established efficacy in metastatic breast cancer (MBC) with distinct mechanism of action. Oral vinorelbine (OVRL) interacts with tubulin and capecitabine (XLD) acts through antimetabolite properties of 5FU. OVRL is rapidly absorbed (1.5- 3h) with elimination half-life around of 40h. No pharmacokinetic interaction was found between these two compounds and its metabolites according to a recent phase I trial. Methods: The treatment schedule was 60 mg/m2 of OVRL on day 1 and 8; XLD 1000 mg/ m2 bid from day 1 to 14 every 3 weeks. Cycles were repeated if ≥1000/mm3 neutrophils and ≥100000 platelets. In case of ≥ Grade (G) 3 haematological and non haematological toxicity dose adjustments were planned: OVRL from 60 mg/ m2 50 or 40 mg/ m2 and XLD from 1000 mg/ m2 to 900 mg/m2 or 750 mg/ m2 b.i.d. Results: Between June 2003 to December 2005, 29 advanced breast cancer pts were included in this trial. Median age: 64 years [range (42–85)]. PS0: 60, PS1: 40. Eight pts, 9 pts and 12 pts received the combination as 1st line, 2nd line and ≥3rd line treatment respectively. A median of 5 cycles [1–30] was given. No G 3/4 haematological toxicity was observed. One pt. suffered from G3 diarrhoea, G2 mild diarrhoea and abdominal pain was reported after ORVRL lasting 24 hours. No hand-foot syndrome has been observed.Out of 18 evaluable pts, 17 had clinical benefit: 1 CR, 4 PR and 12 SD (90% of tumour control). Conclusion: Oral vinorelbine and capecitabine combination is well tolerated and active in MCB pts allowing long-term treatment in ambulatory setting avoiding central venous line and infusions; therefore, this combination should be investigated in early lines of treatment. Final results will be presented during the meeting.

[Table: see text]
Phase II study of gemcitabine (Gem) and trastuzumab (T) combination therapy in first line metastatic breast cancer (MBC) patients (pts) with HER2 overexpression
Authors: Brufsky A. M. , Fox K. , Orlando M. , Abraham J. , Tan-Chiu E. , Haney L. , Wang Y.
Published: March 2020

10591

Background: Phase III studies have demonstrated that the addition of T to chemo is associated with higher response rates (RR), improved time-to-progression (TTP) and improved overall survival in pts with metastatic HER2+ tumors. The greatest benefit from T-based therapy is found in women with pronounced HER2 overexpression (FISH+ or IHC 3+). Preclinical models suggest that Gem+T appear to be additive or synergistic. The present study was designed to determine overall RR (primary endpoint), TTP, OS and the toxicity profile of the combination of Gem+T as first-line therapy for MBC pts. Methods: Pts with measurable HER2-overexpressing (IHC 3+ or FISH+) MBC, no prior chemo in the metastatic setting (adjuvant was allowed), adequate end-organ function and PS 0–2, received Gem 1,250 mg/m2 on days 1 and 8 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. A Simon’s optimal two-stage design was used with a total sample size of 66 (25 patients treated in the first stage and 41 additional patients in the second stage). Results: Sixty-six patients have been treated and results are available for sixty-four patients. Median age: 53 years (range 34–83); Race: Caucasian/Other 88%/12%. ER status positive/negative: 53%/47%. HER2 status IHC 3+/FISH+: 58/20 pts.; ECOG PS 0/1/2: 66%/30%/3%; Prior adjuvant therapy: Chemo 39 pts (prior anthra 31, prior taxane 21), Hormonal 32 pts (6 adj, 18 met, 8 both). Total number of cycles = 396; median = 6 (range 1–21). Toxicity was generally modest. Grade 3/4 neutropenia occurred in 11 pts (17%)/7 pts (11%); thrombocytopenia 3pts (5%)/1pt (2%), anemia 3 pts (4.7%)/ 0 pts, and 2 pts with grade 4 transaminase elevation, grade 3 elevated ALT 6 pts (9.4%); no other grade 4 toxicities were recorded. One pt with prior anthra exposure had a grade 2 decrease in left ventricular ejection fraction; no symptomatic cardiac toxicity was recorded. Best Overall RR assessment (N = 64): CR 8 (12.5%), PR 26 (40.6%) for an overall RR of 53.1% (95% CI: 40%-66%). TTP median 6 mo (95% CI: 4.4 -9.7 mo). Survival data not mature at this time. Conclusions: The combination of Gem+T in front-line MBC shows a high response rate with modest toxicity.

[Table: see text]
Combination of paclitaxel and two schedules of gefitinib in patients with metastatic breast cancer
Authors: Cresta S. , Perotti A. , Merlini L. , Mansutti M. , Marchianã A. , Grasselli G. , Bianchini G. , Ferrario C. , Capri G. , Gianni L.
Published: March 2020

10599

Background: The epidermal growth factor receptor (EGFR) may be overexpressed in breast cancer. Inhibition of EGFR signaling by gefitinib (Iressa) enhances the in vitro antitumor activity of many cytotoxic drugs including paclitaxel. Methods: In this phase II study patients (pts) with measurable metastatic breast cancer and maximum prior exposure to two chemotherapies were randomized to paclitaxel (100 mg/m2 on days 1, 8 q21) and continuous gefitinib, 250 mg daily for 21 days (arm A); or paclitaxel (100 mg/m2 on days 8, 15 q21) with gefitinib 250 mg daily from day 1 to 15 (arm B). Therapy continued for at least 4 cycles after best response. After 6 cycles, responding pts continued with gefitinib monotherapy until progression or unacceptable toxicity. Results: 16 pts in arm A and 17 in arm B were enrolled; 25 had visceral disease (12 in arm A and 13 in arm B). Median age was 53 years (range 29–70). All but one pt received prior anthracyclines and 9 also prior taxanes. Overall 17 pts responded to therapy (intent to treat analysis; arm A: 62.5%, 95% CI: 35.4–84.8%; arm B: 41.2%, 95% CI: 18.4–67.1%). Disease control (CR+PR+SD) was achieved in 81.3% of pts in arm A and 76.5% in arm B, with 10 and 6 pts who continued with gefitinib monotherapy after completing the combination schedule. Median time to progression was 250 (arm A) and 204 days (arm B), while median response duration was 212 (arm A) and 285 days (arm B). Tolerability was good with either schedule of gefitinib. Diarrhea was frequent (68.8% and 64.7%) and of grade 3–4 severity in 6% of pts in arm A and in arm B. Grade 3–4 neutropenia affected 6% and 12% of pts respectively, and 6% of pts in both arms had a grade 3–4 increase of AST and ALT. Other grade 1–2 adverse events included acneiform rash (100% in arm A and 58.8% in arm B), sensory neuropathy (68.8% and 58.8%), anemia (50.0% and 52.9%), neutropenia (25.0% and 17.6%) and myalgia (37.5% and 41.2%). Conclusions: The combination of paclitaxel with gefitinib given continuously or for 2 out of every 3 weeks is feasible and well tolerated. The discontinuous schedule caused less skin toxicity. The good antitumor activity deserves further studies to identify sensitive subgroups and mechanisms of sensitivity. IRESSA is a trademark of the AstraZeneca group of companies.

[Table: see text]
Mature data on neoadjuvant capecitabine chemoradiation (X-RT) for patients (pts) with locally advanced breast cancer (LABC) failing anthracycline-based neoadjuvant therapy
Authors: Gaui M. , Amorim G. , Arcuri R. , Pereira G. , Moreira D. , Djahjah C.
Published: March 2020

10603

Background: In Brazil, LABC remains a serious health problem, representing approx. 30% of all newly diagnosed breast cancers. Anthracycline-based neoadjuvant therapy is a standard treatment, but around 30% of pts do not respond. There is no standard approach in these refractory pts. In our institution, these pts receive RT, but almost half (46%) of pts are not rendered operable by RT alone. Because X is the reference treatment for anthracycline- and/or taxane-pretreated MBC and X and RT are supra-additive in in vivo models, there is a clear rationale for evaluating X-RT in this setting. Methods: Pts eligible for this prospective, open-label, single-center, non-randomized study had inoperable LABC refractory to FAC, ECOG PS ≥1 and adequate organ functions. Pts received RT 20c Gy/d ×5w (total dose 50Gy) plus X 850mg/m2 bid orally d1–14, q3w for 2 cycles. Pts underwent surgery, if possible, after completion of neoadjuvant therapy. Pts with hormone receptor-positive tumors received tamoxifen after surgery. Results: Baseline characteristics of the 30 pts enrolled between Jan 2003 and May 2004: median age 47 years (range, 26–70); median ECOG PS 1; median tumor size (after anthracyclines) 80 cm2 (range, 36–357cm2); tumor grade II/III/unknown 20/37/43%; inflammatory carcinoma 21%. Two pts were excluded from this analysis as they received the incorrect X dosing regimen. 23/28 evaluable pts (82%) were operable after X-RT; 4 (14%) pts did not undergo surgery because of disease progression. Median tumor size after X-RT was 49 cm2 (range, 6–196 cm2). The median relative reduction in tumor size was 33%. After surgery, median residual tumor size was 12 cm2 (range, 0−72) and the median number of positive nodes was 2 (range, 0−27). Pathological complete response was observed in 3 (11%) pts. The most common treatment-related adverse events (all grade 1/2) were mucositis, diarrhea, nausea and emesis. There were no grade 3/4 events. Conclusions: Our data indicate that neoadjuvant X-RT is feasible, well tolerated and appears more effective than RT alone in pts with LABC refractory to FAC, rendering a high proportion (82%) of pts eligible for surgery.

No significant financial relationships to disclose.
The effect of oral vinorelbine and capecitabine in patients with metastatic breast cancer
Authors: Finek J. , Holubec L. , Elgrova L. , Pesta M. , Votavova M. , Pavlikova I. , Frank M. , Bustova I. , Siffnerova H. , Sediva M.
Published: March 2020

10605

Background: Optimal chemotherapy (CT) for advanced breast cancer treatment should be effective, well tolerated and convenient. Although the optimum CT is not defined, oral chemotherapy is an attractive option for many patients. Methods: We report a phase II multicentric study, first and second line metastatic breast cancer (MBC) treatment, at least one measurable lesion, prospectively collected data between 2003 and 2005. Treatment schedule: vinorelbine 60 mg/m2 p.o. day 1 and 8, capecitabine 1000 mg/m2 twice daily, day 1–14 q 21 days. Patients: 84 patients with MBC have been registered. Mean age 58.1 years, ranges (39.7 years–71.9 years). All patients had received prior adjuvant anthracycline based chemotherapy (CT). No adjuvant or palliative CT within the last 12 months, no concomitant hormonal treatment. Results: The median number of oral chemotherapy cycles vinorelbine plus capecitabine was 6 cycles (ranges 1 cycle - 19 cycles), total number of cycles was 550. In 84 evaluable pts the objective tumor response was achieved in 46 pts 55%, (ORR = CR + PR), complete response CR was achieved in 11 (13%) pts, partial response in 35 pts (42%), stable disease in 26 pts (31%). Median follow up was 9.7 months. In the intent-to-treat analysis, median time to progression was 6.7 months, median survival not reached, 58 pts (69%) are still alive. Reported NCI grade 3 - 4 toxicities: neutropenia in 4 pts (5%), febrile neutropenia in 4 pts (5%), vomiting in 6 pts (7%) Conclusion: Oral vinorelbine-capecitabine combination shows very promising activity and low toxicity in the MBC treatment.

No significant financial relationships to disclose.
Pilot study of regional hepatic intra-arterial (HIA) paclitaxel in patients (Pts) with breast carcinoma metastatic to the liver
Authors: Mavligit G. , Kurzrock R. , Cheung A. , Gupta S. , Madoff D. C. , Wallace M. , Kim E. , Curley S. A. , Hortobagyi G. N. , Camacho L. H.
Published: March 2020

10626

Background: Approximately 50% of pts with metastatic breast carcinoma develop hepatic involvement during the course of their disease. Their median survival is 1–14 months (mo). Systemic paclitaxel has good anti-tumor activity against breast carcinoma and is safe. We sought to prospectively determine the safety and anti-tumor activity of HIA paclitaxel therapy. Methods: Ten pts with breast carcinoma and dominant liver metastases received monthly inpatient 24 hr-continuous HIA infusions of paclitaxel at 200 mg/m2 through intra-arterial catheters placed via percutaneous transfemoral approach. WHO tumor assessment guidelines were used. Results: Nine pts enrolled in this study had infiltrating ductal carcinoma and their median age at the time of treatment was 51 years. The group had received a mean of 3.8 previous treatment regimens including adjuvant regimens. Therapy was well tolerated. Fifty-six courses were delivered. Mean hospital stay was 3 days. No procedure related complications were observed. Most common treatment related toxicities included leukopenia, fatigue, nausea, and vomiting. Three pts attained partial responses (50% decrease in tumors) lasting 6, 7, and 48 months whereas in 4 others disease stabilization lasted 5 to 9 mo. One pt underwent liver resection and remained NED for 48 mo. Eight pts had received prior systemic taxane therapy alone or in combination with other cytotoxics (3 adjuvant; 5 palliative). However, no association between previous taxane exposure and clinical efficacy of this regimen was not established. Conclusions: Hepatic arterial therapy with paclitaxel at this dose and schedule is safe and well tolerated and has reasonable anti-tumor activity against breast carcinoma involving the liver. Previous taxane exposure does not hamper the potential benefit of this approach. This regimen deserves further investigation alone or in combination with targeted strategies in patients with dominant liver involvement from breast carcinoma.

No significant financial relationships to disclose.
Study of association between p53 mutation and tamoxifen therapy in women with hormone receptor positive invasive ductal cancer
Authors: Varadarajan R. , Das G. , Janarthanan B. , Desouki M. , Kulkarni S. , Geradts J.
Published: March 2020

10630

Background: ERα promotes cell proliferation in breast tumors whereas p53 impedes cell cycle progression. We have reported direct link between these two opposing pathways. Our preclinical studies have demonstrated that ERα binds directly to p53 and negatively regulates its function and that anti estrogens disrupted the ERα- p53 interaction. Previous retrospective studies by us and others in advanced breast cancer patients had shown presence of wild type p53 in ER+ve breast tumors is associated with better response to endocrine therapy. Objective: To demonstrate women with hormonal receptor(ER) +ve non-metastatic invasive ductal cancer (IDC) with wild type p53 in the tumor tissue will have better DFS and/or OS with tamoxifen compared to those with abnormal p53. Methods: Tissue micro array (TMA) from archival tumor tissue of patients with IDC seen at Roswell Park Cancer Institute (RPCI) between 1992 and 2001 was made. The p53 status was assessed by IHC staining of the TMA, was considered positive (abnormal) if ≥10% nuclear staining was noted. Only those patients in TMA with the following criteria were included for this report; non-metastatic IDC treated at RPCI, patients who received adjuvant tamoxifen (for ER+ve tumors), p53 IHC data available. Results: 83 patients in the TMA with ER+ve tumors who were treated with tamoxifen met the study criteria to test our hypothesis. 35 patients with ER-ve tumors were analyzed to evaluate p53 effect unrelated to p53-ER interaction. Median follow up was 5 years. 16/83 (19%) ER+ve tumors and 11/35 (31%) ER-ve tumors had abnormal p53. 14 (17%) ER+ve and 11(31%) ER-ve patients experienced recurrence. 16(19%) ER+ve and 6(17%) ER-ve patients died (all causes) during the follow up period. Univariate analysis with respect to p53 for OS and DFS were undertaken. No significant OS or DFS difference were noted between patients with tumor tissue wild type and abnormal p53, for both ER+ve or ER-ve tumors. Conclusions: This study does not show any difference in outcome with tamoxifen therapy between tumors with wild type and abnormal p53. A Study with larger sample size involving sequence analysis and IHC is required to conclusively demonstrate the effect of the two common occurrences (ER+ve and abnormal p53) and tamoxifen.

No significant financial relationships to disclose.
Gemcitabine plus carboplatin for patients with pretreated, metastatic breast cancer: A phase II trial
Authors: Laessig D. , Vehling-Kaiser U. , Fasching P. , Melchert F. , Koelbl H. , Stauch M. , Maubach P. , Scharl A. , Stemmler J. , Heinemann V.
Published: March 2020

10635

Background: In search for treatment regimens which can be applied in anthracycline- and taxane-pretreated patients, the combination of gemcitabine and cisplatin was shown to be effective in several trials. To improve on tolerability and handling of the regimen, cisplatin was replaced by carboplatin in the present trial. Methods: Patients with intensively pretreated, metastatic breast cancer (age 18 to 70 years) and measurable disease were treated with gemcitabine (1000 mg/m2 iv on days 1 and 8) and carboplatin (AUC 4 iv on day 1) in a 3-week regimen. The trial was performed as a 2-stage phase II study according to the optimal design described by Simon (p0 = 0.1, p1 = 0.3, α = 0.05, β = 0.1) with overall remission rate (according to RECIST) as the the primary objective. Results: Of 39 recruited patients (median age: 60 years, range 29 to 77 years) response data are available from 35 patients. A positive hormone receptor status was observed in 77% of patients, and 31% of patients were Her-2 overexpressing. All patients had received prior chemotherapy, and 49% of patients had been subjected to 2 or more treatment regimens for metastastatic disease. Prior treatment consisted of anthracyclines (87%), alkylating agents (77%), taxanes (67%), and antimetabolites (62%). Prior endocrine therapy had been applied to 77% of patients. At the time of evaluation, a total of 183 treatment cycles were documented with a median number of 5 cycles per patient (range 1 to 11). Treatment is presently ongoing in 8 patients. A CR was observed in 1/35 patients, a PR in 8/35 patients for an overall remission rate of 26% (95%-CI: 12% to 43%). Stable disease was documented in 49% (17/35) of patients. Median time to progression was 4.9 months (95%-CI: 2.9 to 6.8 months). In 39 evaluable pts, CTC grade 3/4 leukopenia was observed in 22/2 pts, neutropenia in 14/8 pts, anemia in 3/0 pts, and thrombocytopenia in 11/8 pts. Treatment delays and/or dose reductions were performed in 49% of cycles. Conclusion: Gemcitabine in combination with carboplatin is an effective combination for second- or third-line treatment in patients with metastatic breast cancer.

[Table: see text]
Human chorionic gonadotropin (HCG) induction of apoptosis in breast cancer
Authors: Carter W. B. , Sekharam M.
Published: March 2020

10658

Background: Apoptotic induction in cancer cells may improve the efficacy of local or systemic therapy. Human Chorionic Gonadotropin (HCG) injection directly into Kaposi’s sarcoma or melanoma has been shown to increase the apoptotic index in these tumor types. The rapid induction of apoptosis in breast cancer immediately preceding local or systemic therapy may improve the response to therapy or local control. We hypothesized that HCG would rapidly increase the apoptotic index in breast cancer after intratumoral injection. The primary objective of this preclinical trial was to determine if intratumoral injection of HCG would significantly increase the apoptotic index in breast cancer xenografts. Methods: Using a human breast cancer xenograft model in Nude mice, 5 × 106 SK-BR3 human breast cancer cells were injected subcutaneously into each flank of nu/nu mice. When the tumors reached 6 mm, 50 uL (100 U/mL) of non-recombinant, naturally occuring HCG (A.P.L., Wyeth) or saline vehicle control was injected directly into the xenograft tumors. After 24 hrs, the tumors were harvested, and the xenografts tested for proliferation (Ki-67) and apoptosis (by TUNEL assay). The apoptotic index was calculated (apoptosis/proliferation) and statistical analysis performed using paired T-test. Results: Seven pairs of SK-Br3 xenografts were tested. There were no differences in proliferation by Ki-67 determination between control or treated xenografts. Apoptosis increased in HCG treated xenografts compared to vehicle controls. Apoptosis increased from a mean of 5% (range 1– 20%) in control xenografts to a mean of 28% (range 1–70%) in HCG treated tumors (p = 0.038). Conclusions: Naturally-derived HCG induces apoptosis in human breast cancer xenografts after intratumoral injection. Substantial induction of apoptosis may improve the efficacy of local and systemic therapy in breast cancer. Injection of HCG into breast tumors immediately prior to surgical, radiation, or systemic therapy has the potential to improve local control or response to treatment. Futher elucidation of potential synergy with therapeutic modalities is justified.

No significant financial relationships to disclose.
Phase II study of an epirubicin and docetaxel (ET) combination as pre and post-operative systemic therapy in patients with early stage breast cancer (EBC)
Authors: Nishimura R. , Rai Y. , Mitsuyama S. , Toyoshima S. , Iwasaki H. , Ichinose I. , Tamura K. , Matsuo F. , Hara S. , Yano H.
Published: March 2020

10660

Background: The goal of chemotherapy (CT) for EBC is to achieve a high pathologic complete response (CR) leading to an increase in the rate of breast conserving surgery (BCS). ET is one of the most active CT regimens for metastatic breast cancer. The primary endpoint of this study was to evaluate clinical response Methods: Eligible patients (pts) were newly diagnosed with EBC and had large primary tumors (stage II-III, > 3 cm). Forty-seven pts were enrolled and received epirubicin 60 mg/m2 followed by docetaxel 60 mg/m2 every 3 weeks for 4 cycles before surgery. Within 4 weeks after surgery, 4 additional cycles of ET were given to the pts who responded to ET. Results: Forty-five pts were evaluable for safety and clinical response. The median age was 47 (range, 29–75). The tumor size was T2 in 44% of the pts, T3 in 36%, and T4 in 20%. ER and PgR were both positive in 40% of pts, while both negative in 31%. HER2 was positive in 33% of pts. Four cycles of ET at full dose were given to 96% of pts prior to surgery. The clinical response was 73% including 7% CR (95% CI 58–85%); the BCS rate was 36%. Central pathologic review was performed in 37 pts showing disappearance of all tumor cells (grade 1) in 1 patient (3%) and 2 pts (5%) achieved a grade 2 response (in situ carcinoma in the operated breast) by Chevallier’s criteria. Grade 3–4 toxicities included neutropenia (71%), leukocytopenia (69%), febrile neutropenia (18%) and anorexia (9%). Twenty-four of 33 pts who responded to ET received additional ET after surgery. Conclusions: ET showed a high clinical response in previously untreated EBC with acceptable toxicity. In order to improve pathological CRs further, the doses and treatment schedule of this regimen needs to be improved. Currently, we are following the pts to assess differences in survival between pts with or without additional adjuvant ET.

No significant financial relationships to disclose.
Oral vinorelbine plus capecitabine (oral vincap) combination in patients with advanced breast cancer (ABC)
Authors: Lorusso V. , Spada M. , Giampaglia M. , Misino A. , Calabrese R. , Latorre A. , Monticelli G. , Guida M. , Sambiasi D.
Published: March 2020

10673

Background: Vinorelbine i.v. and capecitabine are two of the most effective single agents in previously treated advanced breast cancer (ABC). A number of studies have been reported with the combination of these agents. Actually, the availability of oral formulation for vinorelbine allows a full oral combination of the two agents. The aim of this study was to evaluate the activity and toxicity of this novel combination. Patients and Methods: Thirty-eight advanced breast cancer patients (pts) refractory to anthracyclines and taxanes were included in this study. Treatment consisted of vinorelbine 60 mg/m2 (days 1 + 8), and capecitabine 2000 mg/m2 (days 2–7 and 9–16) every 3 weeks. The pt characteristics were: median age 53 years (range 37–77 years); ECOG PS 0–1 in 35 pts (92.1%), and PS 2 in 3 pts (7.8%); ER+/PgR+ 20 pts (52.6%) and ER−/PgR− 11 pts (28.9%). Dominant sites of disease were visceral in 19 pts (50.0%), bone in 10 pts (26.3%), soft tissue in 9 pts (23.6%). Results: A total of 228 courses were given with a mean of three cycles/pt (range 1–12). Five pts (13.1%) had no toxicity at all. Hematologic side-effects were: neutropenia G2-G3 in 7 pts (18.9%), and G4 in 1 pt (2.7%), anemia G1 in 11 pts (29.7%), G2-G3 in 5 pts (13.5%), thrombocytopenia G1 in 6 pts (16.2%) and G3 in 1 pt (2.7%). Non-hematologic side-effects were: fatigue G1 in 5 pts (13.5%), hand-foot syndrome G1 in 2 pt (5.4%) and G2 in 2 pts (5.4%), nausea/vomiting G1 in 2 pts (5.4%), G2 in 3 pts (8.1%) and G3 in 1 pt (2.7%), constipation G1 in 2 pts (5.4%), peripheral neurotoxicity G1 in 3 pts (8.1%) and G2 in 1 pt (2.7%), gastric pain G1 in 2 pts (5.4%), stomatitis G1 in 3 pts (8.1%) and G2 in 1 pt (2.7%). Out of 38 pts assessable, we observed 2 (5.4%) CR, 13 (34 %) PR, 14 (37.8%) SD, and 9 (26.3%) PD. The median time to progression was 4.5 months (range 1–18 months), the median response duration was 7 months (range 2–18 months), and the median survival duration was 10 months (range 2–26+). Conclusions: The oral vincap combination was well tolerated and effective in ABC. In fact, this regimen achieved results comparable to the previously reported combinations of capecitabine and i.v. vinorelbine. The oral vincap should be considered as an alternative to single agent capecitabine or vinorelbine in ABC refractory to antra-taxane combination.

No significant financial relationships to disclose.
Preliminary results of a phase II study of neoadjuvant treatment with docetaxel (T), doxorubicin (A) and capecitabine (X) in locally advanced or inflammatory breast cancer (LABC)
Authors: Perez Manga G. , Méndez M. , Palomero M. I. , Quibén R. , Belón J.
Published: March 2020

10678

Background: Previous studies suggest that combined treatment of chemotherapy + surgery + radiotherapy has a high survival rate in pts with locally advanced or inflammatory breast cancer. Primary objective was evaluate response rate. Secondary objectives were time to progression and toxicity profile of neoadjuvant chemotherapy T, A and X in pts with LABC. Methods: Eligibility criteria: Pts with histological confirmation of LABC, ECOG PS ≤ 2, age ≤ 75 years, LVEF > 50%, and adequate bone marrow, renal and hepatic function. Prior systemic therapy, surgery or radiotherapy for breast cancer was not allowed. Pts with invasive bilateral breast cancer were not included. Treatment: T (30 mg/m2) iv day 1, 8 and 15, A (50 mg/m2) iv day 1 and X (1500 mg/m2 o.d.) days 1–14, in a 4 weeks course. This scheme was repeated up to 4 cycles followed by surgery. According to investigator criteria pts receive a maximum of six cycles. Radiotherapy and hormonal treatment are allowed depending on molecular markers. Expression of markers was performed by inmunohistochemistry before chemotherapy. Results: 36 pts were included in this analysis, with a median age of 48 years (25–69). ECOG PS was 0 in 32% of pts and 1 in 68%. Hormonal receptor status was ER+ 43%, PR+ 34% and C-erb2+ 52%. A total of 131 cycles (median 4, range 1–4) were administered. Median relative dose intensity was 86% for T, 91% for A and 93% for X. Two patients are still undergoing treatment; of 34 evaluable pts for efficacy, 11 achieved CR, 22 PR and 1 PD resulting in an ORR of 97% (CI 95%: 92–100). Surgery was performed in 34 pts: 3 (9%) of them achieved pathological CR and one additional patient had non invasive carcinoma. Grade III/IV toxicity per patient was neutropenia (69%), leucopenia (53%), febrile neutropenia (8%), mucositis (14%), diarrhea (11%), nausea/vomiting (6%), dysgeusia (3%) and asthenia (3%). Median follow up time was 8.8 months. Conclusions: T, A and X every 28 days administered during 4 cycles as neoadjuvant chemotherapy in LABC is an active regimen with a manageable toxicity profile before surgery.

No significant financial relationships to disclose.
Introducing a new scoring system based on HER2/neu, p53 oncogenes results and mammographic findings for prediction of tumor grade in breast cancer
Authors: Guity M. , Mokri M. , Shakiba M. , Atri M.
Published: March 2020

10687

Background: During recent years, several oncogenes have been introduced in relation to breast cancer including her2 and P53. These are related with initiation, degree of progression, invasion and prognosis of breast cancer. In this research the rate of positivity of these oncogenes in 150 patients with invasive ductal carcinoma is introduced and the correlation of the results of a new scoring system comprised of mammograms, P53 and her2 with the tumor grade is assessed. Methods: 150 cases of invasive ductal carcinoma of a private clinic were chosen. The diagnosis of cancer and its grade was confirmed by pathology. All patients underwent mammography befor surgery and the results were classified according to BIRADS system to benign (groups of I and II in BIRADS): Score I, suspicious (group III in BIRADS): Score II and malignant (groups of IV and V in BIRADS): score III. P53 and her2 presence were assessed by immunohistochemical studies and the results were classified as negative (score I) and positive (score II). The final score of each patients was calculated by adding scores of all three studies (P53, her2, mammography) which ranged between 3 to 7. Results: The average age of the patients was 48.2 + 11.2 years; most of them were between 30–50 years old. Three had benign mammograms (2%), 81 had suspicious (54%) and 66 had malignant findings (44%). We showed positive P53in 59 (39%), positive her2 in 69 (46%) and high grade tumor in 77 (51%) patients. On scoring, 2 patients gained 3 (1.3%), 36 scored 4 (24%), 53 patients received 5 (35.3%), 37 reached 6 scores (24.7%) and 22 patients received 7 scores (14.7%). Placing scores 3 and 4 in one group and scores 5–7 in another, the sensitivity and negative predictive value of the system for high grade tumors reached 97.7% and 89.5% respectively. By placing scores 3–6 in one group and score 7 in another, the specificity and positive predictive value of the system reached to 100%. Conclusions: The results of mammography, P53 and her2 seems to have a good correlation with tumor grade, meaning when all three parameters are positive, the patients’ tumor is almost always high grade.

No significant financial relationships to disclose.
High dose chemotherapy with autologous stem cell rescue as a part of combined modality therapy in stage IIIB inflammatory breast cancer
Authors: Farjami S. , Waheed F. , Liu D. , Seiter K. , Ahmed T.
Published: March 2020

10694

Background: Despite the improvements related to introduction of neoadjuvant chemotherapy, the prognosis of patients with inflammatory breast cancer remains poor. The purpose of this study was to evaluate the efficacy, feasibility and outcomes of high dose chemotherapy in this group of patients. Methods: Between June 1991 and January 1999, twenty eight patients with pathologically confirmed inflammatory breast cancer were consecutively enrolled in this study. All patients were rendered free of clinically evident disease by using chemotherapy (adjuvant, neoadjuvant or both) either alone or in combination with surgery. Following stem cell collection patients received HD-CT with thiotepa 250mg/m2 days 1, 2 & 3(total dose of 750mg/m2), mitoxantrone 40mg/m2 on day 1 and carboplatin 333mg/m2 on days 1, 2 & 3 ( total dose of 1gm/m2). Previously stored stem cells were infused on the seventh day of HD-CT chemotherapy. Eligible patients received radiation to the chest wall and tamoxifen for 5 years. Results: With median duration of follow-up of 46.9 months( range 15.1–177.2), the median overall survival (OS) and progression free survival (PFS) were 42.5 months (range 9.7–135.7) and 34.8 months (range 3.3–135.7), respectively. The multivariate analysis showed a significantly better EFS and OS in patients with estrogen receptor (ER) positive tumors ( P value ≥ 0.003). Mucositis and Infection were the most severe non-hematological toxicities. Grade four cardiac and pulmonary toxicities developed in one patient. There was no transplant related mortality. One patient developed myelodysplastic syndrome. Conclusions: The results of our study suggest that high dose chemotherapy with thiotepa, mitoxantrone and carboplatin is a safe and efficacious regimen in patients with stage IIIB inflammatory breast cancer.

No significant financial relationships to disclose.
Axillary recurrence after negative sentinel node biopsy in patients with breast cancer
Authors: Cassanello G. E. , Xynos F. , Capellino P. H. , Bacigaluppi A. , Betti P.
Published: March 2020

10700

Background: To evaluate axillary recurrences (AR) in patients with negative sentinel node subjected to no further axillary local treatment. Methods: From June 1st 2000 to April 30th 2005, 219 patients with negative sentinel node (SN) were evaluated and axillary recurrences were assessed. The SN was identified using Isosulfan Blue only. The lymph nodes were evaluated intraoperatively with imprint cytology and with standard H&E staining on permanent sections, sectioning lymph nodes every 3 mm. The false negative of imprint cytology was 6%. The mean age was 69.8 years (range 40–90), the average follow up was 17.6 months (range 1–48). Results: Three axillary recurrences (1.36%) and no distant metastasis were observed. The recurrences occurred 14,26 and 28 months after conservative treatment for ductal carcinoma with 1, 2 and 3 negative sentinel nodes respectively. At the time of recurrence axillary surgery revealed 1 of 11 positive axillary nodes with extra-capsular invasion, 6 of 19 positive axillary nodes with extracapsular invasion and 3 of 15 positive axillary nodes with extracapsular invasion Conclusions: In this short follow-up three axillary recurrence (1.36%) and no distant metastasis have been observed. In the case of axillary recurrences, extracapsular node invasion seems to be the rule.

No significant financial relationships to disclose.
CEA as a prognostic factor in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy
Authors: Valeri N. , Battelli N. , Mariotti C. , Santinelli A. , Siquini W. , Gusella P. , Braconi C. , Lippe P. , Cascinu Prof S.
Published: March 2020

10705

Background: CEA and CA 15.3 are most commonly used to evaluate disease progression in metastatic and recurrent breast cancer. Only few significant studies showed a potential predictive role of CEA and CA 15.3 in adjuvant or neoadjuvant setting. We evaluated the correlation between tumour markers level at diagnosis and outcome in locally advanced breast cancer patients treated with neoadjuvant chemotherapy. Methods: Patients with locally advanced breast cancer (T > 3.5 cm and T4) at diagnosis entered the study. All patients had to have initial negative staging (chest X-ray, abdominal ultrasonography, bone scintigraphy and CT scan), whereas all patients who developed metastatic disease in sites which were uncertain during initial staging were excluded. Tumour markers at diagnosis were considered negative if CEA was inferior to 5 ng/ml and CA 15.3 inferior to 35 U/ml. All patients received neoadjuvant chemotherapy (4–6 cycles with regimens containing Anthracyclines and Taxanes or FEC). Most of patients underwent radical mastectomy followed by sequential radiation therapy and adjuvant chemotherapy and/or hormonotherapy in hormonal responsive patients. Results: Fifty-three patients entered the study. At a median follow up of 73 months, 35 patients were disease free after adjuvant treatment (group A), whereas 18 patients developed metastatic disease during follow-up (group B). At diagnosis 14 patients had CA 15.3 greater than 34 U/ml (7 in group A and 7 in group B), 6 patients had CEA greater than 5 ng/ml (1 in group A and 5 in group B) and 18 patients had CEA or CA 15.3 greater than normal values (7 in group A and 11 in group B).We analyzed DFS and OS in patients with normal (CEA < 5 ng/ml, CA15.3 < 35 U/ml) and elevated (CEA ≥ 5 ng/ml, CA 15.3 ≥ 35 U/ml) tumour markers at diagnosis; DFS (p = 0.001) and OS (p = 0.03) were significantly reduced in patients with elevated CEA at diagnosis; differences were not statistically significant for CA 15.3 (p > 0.05). Conclusions: CEA levels before neoadjuvant treatment could represent an important prognostic factor and may influence the choice of treatment in locally advanced breast cancer patients .

No significant financial relationships to disclose.