bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjuvant trastuzumab (T) therapy in HER2+ breast cancer after ASCO 2005: Patients’ attitudes and immediate economic burden
Authors: Benn S. M. , Jha G. , Ratliff T. W. , Spiers K. , Baskin R. , Yunus F. , Osarogiagbon R. , Boston B. , Minhas S. , Jahanzeb M.
Published: March 2020

10565

Background: Data from 3 large randomized trials documenting the efficacy of T in the adjuvant setting were reported at ASCO 2005, and subsequently published in NEJM 2005; 353: (16) pp 1659–72 and 1673–1684 . We decided to offer T, and attempted to assess patients’ characteristics that influence its acceptance, in a subgroup of HER2 + patients that had already completed adjuvant chemotherapy at our institution within 12 months prior to these reported results. Methods: Using Electronic Medical Records (OpTx, Canada), we identified HER2+ breast cancer patients who had completed adjuvant therapy within the prior 12 months and administered an informational synopsis about the study results. They then completed a questionnaire, including their demographic information, that established their understanding of the data and documented their decision to receive or to not receive adjuvant T as an afterthought. Results: We identified 1442 breast cancer patients in Optx that were seen at UTCI for initial or follow up visits between May 2004 and May 2005. Those with 3 or fewer visits within the last year and those who received no chemotherapy (n = 770) were excluded. Of the remaining 672 patients, only 104 (15%) had documented HER2+ disease. Fourteen HER2+ patients had metastatic disease, while 84 patients, though HER2+, had either completed adjuvant chemotherapy greater than 12 months prior or were currently receiving adjuvant therapy or T, and/or had other reasons to not be suitable for T. Six patients qualified for this study; 5 decided to receive adjuvant T and 1 chose not to because she perceived the additional benefit to be minimal. Conclusions: While our sample size was too small in the end to draw conclusions about patients’ attitudes towards new data on adjuvant T, we were struck by the small number of patients who could be offered T as an afterthought despite our large patient volume. The magnitude of the perceived economic burden and its imminence after the release of these data may have been overestimated.

[Table: see text]
Nitric oxide and asymmetric dimethylarginine (ADMA) in malignancy associated thrombosis and their modulation by anticoagulants
Authors: Fareed J. , Hoppensteadt D. A. , Demir M. , Iqbal O. , Jeske W. , Tobu M. , Bick R.
Published: March 2020

10573

Background: Cancer associated thrombotic complications are primarily due to endothelial dysfunction and upregulation of inflammatory processes. Nitric oxide (NO) represents one of the major endothelial derived vasoactive mediators. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase which inhibits NO production at pathophysiologic levels. Plasma ADMA levels are upregulated in atherosclerosis, hypertension, end stage renal disease, chronic heart failure and microangiopathy. Methods: To test the hypothesis that endothelial dysfunction in cancer patients may result in increased ADMA levels, plasma samples were retrospectively analyzed from an open label, multidose, active comparator designed study in which all patients (n = 110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1–1.5 mg/kg sc for 5 days and further subdivided into group E which continued to receive E and warfarin (W) group which was given oral anticoagulants for a period of up to 12 weeks. Baseline blood samples (BL), 5 days post E (IPE) and 4–6 week samples from the E and W were analyzed for ADMA and NO levels by ELISA methods. Results: Both the ADMA and NO levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in the ADMA levels which persisted throughout the treatment period. However, in the W converted group the ADMA levels rebounded to an increased level indicating that E differentially regulated ADMA in these patients. The down regulation pattern of NO was similar for both E and W. Conclusions: These results suggest that patients with cancer and thrombosis exhibit simultaneous upregulation of ADMA and NO. While E and W show a differential regulation of ADMA both result in downregulation of NO. The fact that E regulates ADMA is highly suggestive of its role in iNOS regulation which may be involved in the inflammatory response in cancer patients.

[Table: see text]

No significant financial relationships to disclose.
Preoperative dose-dense sequential chemotherapy of epirubicin/cyclophosphamide followed by docetaxel/capecitabine in patients with early breast cancer
Authors: Iacobelli S. , Cianchetti E. , Ficorella C. , Angelucci D. , Grossi S. , Ricevuto E. , Castrilli G. , Zilli M. , Tinari N. , Natoli C.
Published: March 2020

10598

Background: The use of preoperative chemotherapy for breast cancer has been shown to result in similar disease-free and overall survival as postoperative adjuvant chemotherapy. Additionally, the rate of pathologic complete response (pCR) in the breast after preoperative chemotherapy has been shown to correlate with survival. The objective of this study was to evaluate the activity and safety of a dose-dense and sequential chemotherapy of epirubicin/cyclophosphamide (EC) followed by docetaxel/capecitabine (DXe) given preoperatively in patients with early breast cancer not candidate to breast-conserving surgery. Methods: Forty-one women with histologically/cytologically confirmed primary breast cancer (T2–3, N0–2, M0) received 4 cycles of EC (cyclophosphamide, 600 mg/m2 and epirubicin, 90 mg/m2) q2 weeks followed by two cycles of DXe (docetaxel, 36 mg/m2 days 1, 8, and 15 and capecitabine, 1250 mg/m2 days 5–18) q 28 days, with pegfilgrastim support. The study was designed as a Simon’s two-step phase II study. The primary end point of the study was the incidence of pCR defined as the absence of invasive cancer in the breast at definitive surgery. Results: Thirty-nine out of 41 enrolled patients were evaluable for response to treatment (one patient withdrew from the study for G4 neutropenia after the first EC cycle, and the other for therapy refusal after the 4 EC cycles). A pCR was observed in 10 patients for a total pCR rate of 25.6%. Interestingly, all but one of the 10 pCR cases showed ER/PR-negative/Her2-positive tumors. A clinical response (CR or PR) detected by palpation and by imaging was observed in 37 patients, for an overall response rate of 95%. Twenty-nine patients (75%) underwent breast-conserving surgery. The treatment was well tolerated: one patient experienced G3 mucositis and another patient required a 25% dose reduction of capecitabine because of hand-foot syndrome. There was no case of cardiac toxicity, thrombocytopenia or any other serious adverse event. Conclusions: The dose-dense sequential combination EC/DXe is endowed with good antitumor activity and limited toxicity, allowing a high rate of pCR and breast conservation. Thus, this regimen can be considered for further clinical trial.

No significant financial relationships to disclose.
The risk of breast cancer recurrence in the sentinel lymph node era
Authors: Gold L. P. , Cheng Z. , Tafra L. , Sawyer K. , Verbanac K. , Rosman M.
Published: March 2020

10600

Background: Sentinel lymph node biopsy (SLNB), the preferred method of axillary staging in early breast cancer, is more sensitive and accurate compared to axillary node dissection. However, this data has not been incorporated into current prognostic models estimating the risk of breast cancer recurrence. We hypothesize that prognostic models based on data in the pre-SLN era underestimate survival and exaggerate benefits resulting from adjuvant therapy. In order to evaluate this hypothesis, we examined the disease free survival (DFS) and overall survival (OS) in an IRB approved, prospective, multicenter study of SLNB. Methods: From 1996–2005, 564 patients who had invasive disease in whom a SLN was found were examined from two experienced sites . Data was analyzed with regards to SLN status, tumor size, grade, lymphovascular invasion (LVI), age, estrogen receptor (ER) status and use of chemotherapy with respect to DFS and OS. Results: Median age was 57 years, tumor size was 1.5 (range 0.08–10.5) cm and follow-up was 46.2 (range 1–104.5) months. The SLN was positive in 31.2% of patients. The Kaplan-Meier (K-M) 5 year estimate of OS was 94.5(±1)% and DFS 88(±2)%. Tumor grade and size, LVI, ER- and +SLN significantly correlated with poorer DFS and OS by univariate analysis. By multivariate analysis, however, SLN status was the only statistically significant predictor for DFS (p = 0.004; HR = 3.4; CI = 1.5 - 8.0) and OS (p = 0.0051; HR = 7.3; CI = 1.8–29.4). SLN negative patients showed K-M 5 year DFS and OS estimates of 94(±)% and 97.4(±1)% respectively. There was no significant difference in DFS for SLN- patients treated with or without chemotherapy (p = 0.3). Conclusions: SLN status was the only significant predictor of DFS and OS. In node negative patients, we observed a higher DFS and OS than current statistical models based on historical data would have predicted. In this new era of SLNB, the magnitude of benefit from adjuvant therapy in sentinel node negative patients should be re-evaluated.

No significant financial relationships to disclose.
Positive predictive factors for residual disease in re-excision specimens of early stage breast cancer
Authors: Haideri N. A. , Moormeier J. , Arora N.
Published: March 2020

10604

Background: Breast conservation followed by radiation is the treatment in patients with Stage 0, 1, 2, breast cancer. Patients with positive, close or indeterminate margins on excisional biopsy typically undergo reexcision. Residual tumor is identified in 32% to 62% of reexcision specimens as reported in several studies. Such patients undergo subsequent surgery. This study analyzed the pathological specimens of patients undergoing reexcision, to identify characteristics that may predict residual disease. Methods: Patients with the AJCC Stage 0, 1, 2, were identified from Jan 95–Dec 02 with positive, close or indeterminate/unknown margins. All specimens were inked and patients undergoing reexcision were included. Pathological specimens with positive margins, undergoing reexcision were reviewed. Of the 211 patients studied, 159 were eligible. Age, stage, pathologic type, differentiation, microclacifications, extensive intraductal component, lymphovascular invasion, estrogen receptor status, progesterone receptor status, Her 2 neu, S phase and lymph node involvement were evaluated to predict residual disease. Univariate analysis was performed to evaluate the different variables independently. The P values obtained were 2 sided. Results: 131 (82.3%) specimens with positive margins underwent reexcision. Residual cancer was identified in 66 (41.5%) patients. Well differentiated tumors can be an independent predictor of residual disease based on the P value of 0.025 found in this study. Stage 2B, DCIS, microcalcifications and extensive intraductal component was frequent in re-excision specimens, but not significant. Conclusions: Incidence of residual carcinoma is significant in patients undergoing reexcision, making it difficult to identify a group with positive margins where a reexcision can be avoided. Therefore patients with positive margins should typically undergo reexcision, followed by radiation for comprehensive treatment of their early stage breast cancer.

[Table: see text]

No significant financial relationships to disclose.
Antisense oligonucleotide targeted to the transferrin receptor gene suppresses tumor growth and lung metastases in 4T1 mammary adenocarcinoma mouse model
Authors: Jiang X. , Israyeeyan A. , Boykin E. , Lomax L. , Head J. F. , Elliott R. L.
Published: March 2020

10616

Iron is required for the activity of ribonucleotide reductase and synthesis of DNA. Cellular surface transferrin receptors (TfR) are the principal transport protein for iron into cells. It has been reported that inhibition of TfR gene expression leads to the suppression of tumor cell growth in cell culture. In the present study, an antisense oligonucleotide targeted to the transferrin receptor gene was used to treat 4T1 mammary adenocarinoma in cell culture and a mouse model. The cytotoxicity of a 24-mer TfR antisense oligonucleotide was determined by 3[H]-thymidine incorporation in vitro. The sense and random sequence 24-mer oligonucleotides were used as controls. We found that TfR antisense inhibited mRNA expression of TfR and cell growth of the 4T1 cells in the dose-dependent manner. Mice bearing the 4T1 mammary adenocarcinoma were continuously treated for 14 days through subcutaneous implantation of Alzet osmotic mini-pumps. Tumor sizes were measured twice a week. Tumor necrosis and metastases were determined grossly at autopsy and by microscopy. Tumor metastases to lungs (all lung lobes) was scored by the following criteria: 0 = no metastasis, 1 = 1–2 foci/slide, 2 = 3–10 foci/slide, 3 = 11–20 foci/slide and 4 = >20 foci/slide. At 4, 7 and 10 days post-treatment, tumor sizes of the TfR antisense-treated group were significant smaller than control mice (p < 0.05, p < 0.05 and p < 0.05, respectively). At 14 days post-treatment, autopsy showed that 91.7% (11/12) of control mice had multiple metastatic foci on their lung surfaces, but only 16.7% (2/12) of TfR antisense-treated mice had metastatic tumor foci on their lung surfaces (p < 0.001). Primary tumor did not have significant necrosis in either group. Mean lung metastasis scores of 3.25 ± 1.06 in control group vs. 1.75 ± 1.49 in TfR antisense-treated group (p < 0.01) were determined by microscopy. In summary, TfR antisense inhibited cell growth in cell culture and primary tumor growth in mice, and reduced lung metastasis of the 4T1 mouse mammary adenocarcinoma.

No significant financial relationships to disclose.
Split, low-dose docetaxel (D) and low-dose capecitabine (C) is an active regimen in metastatic breast cancer with minimal toxicity
Authors: Silva O. E. , Lopes G. , Morgensztern D. , Lobo C. , Abdullah S. , Doliny P. , Slingerland J. , Gluck S. , Santos E. , Welsh C. , Hurley J.
Published: March 2020

10618

Background: Successful therapeutic regimens in metastatic breast cancer must balance efficacy and tolerability. D and C is an active and commonly used doublet in this setting. D upregulates thymidine phosphorylase and thus potentiates the anti-tumor effects of C. A schedule with split, low-dose D in combination with low dose C could improve the therapeutic index of this regimen without compromising its clinical activity. Methods: Patients with previously untreated her2-neu negative metastatic breast cancer were included. A Simon 2-stage Phase II clinical trial was designed to assess the response rate (primary end-point), and toxicity of docetaxel 25 mg/m2 on days 1 and 8 in combination with capecitabine 750 mg/m2 bid on days 1–14 of a 21-day cycle. RECIST criteria were used for response assessment, which was performed every 2 cycles. Results: Thirty-one women have been enrolled. Median age was 55. Twenty patients had hormone receptor positive disease. Sites of metastasis were as follows: bone, 24 patients; liver, 14; lungs or pleura 14. A total of 189 cycles have been delivered (median: 4 cycles, range 1–33). Grade 3 and 4 toxicities were as follows: peripheral neuropathy, 2 patients; edema, 1 patient; skin, 1 patient. Two women had fever without neutropenia. Another patient had a gastric perforation but recovered without sequela. Twenty-two patients are available for response evaluation. One patient with a single bone metastasis had a complete response after chemotherapy followed by radiation. Partial responses were seen in 10 patients, for an overall response rate of 50% (95% CI, 30 to 70). Four women had stable disease and 7 had progressed at the time of first assessment. With a median follow-up of 15 months (range 1–26), the median time to treatment failure (all patients) was 7 months (range 1–26+). Median survival has not yet been reached. Out of 8 patients older than 65, seven were evaluable and 4 had a partial response. Conclusions: Split, low-dose Docetaxel and low-dose Capecitabine is an effective combination in the first-line treatment of patients with metastatic breast cancer. Toxicity with this schedule was minimal, making it an attractive regimen for further study.

[Table: see text]
A population-based study of trastuzumab-mediated cardiotoxicity among early stage breast cancer patients treated with adjuvant trastuzumab
Authors: McArthur H. L. , Barnett J. , Chia S.
Published: March 2020

10640

Background: Given the risk of cardiotoxicity demonstrated with trastuzumab (T) in the MBC literature, adjuvant T trials incorporated stringent cardiac monitoring. In 2005, several of these trials were reported with impressive DFS improvements. As a result of these trials, women in the province of British Columbia with HER-2 positive early stage breast cancer were offered T either concurrently or sequentially with their primary chemotherapy regimen. Given the paucity of data surrounding adjuvant T-mediated cardiotoxicity among the general population, we performed a retrospective review of cardiac toxicity among all patients receiving adjuvant T at the BCCA. Methods: Patients receiving adjuvant T between July 1, 2005 and December 31, 2005 either sequentially or concurrently with their primary chemotherapy regimen were identified by screening the BCCA pharmacy database. A chart review was conducted and the T start date; LVEF values at 0, 3 and 6 months; and patients with symptoms suggestive of congestive heart failure were identified. The mean LVEF values at 0, 3 and 6 months were calculated. Results: 133 patients received adjuvant T alone after completing their primary chemotherapy. The mean baseline LVEF was 60.5%. Of the 101 and 11 patients available for analysis at 3 and 6 months, the mean LVEF was 58.5% and 58.4%, respectively. 5 patients (3.8%) developed symptoms of CHF. 58 patients received adjuvant T concurrently with their primary chemotherapy (four cycles of AC followed by four cycles of concurrent paclitaxel and T). Of these, only 18 patients had an LVEF measured at 0 and 3 months, with a mean LVEF of 64.6% and 63.6%, respectively. Of the 7 patients who also had an LVEF measured at 6 months, the mean was 60.5% for an absolute decrease of 4.1% from baseline. One patient (1.7%) had symptomatic CHF. Conclusions: A clinically meaningful rate of cardiotoxicity is seen with both sequential and concurrent adjuvant T. In particular, we have demonstrated a higher rate of cardiotoxicity with adjuvant T alone than was observed in the HERA trial. These findings support ongoing stringent cardiac monitoring among the general population treated with adjuvant T.

[Table: see text]
Routine staging radiology is not needed for all breast cancer patients
Authors: Kell M. R. , Healy C. , Martin Z. , Downey R. , Potter-Bierne S. , Gorey T. F. , Flannigan F. , Stokes M.
Published: March 2020

10648

Background: Early stage breast carcinoma is unlikely to have undergone metastatic spread at the time of presentation. The utility of routine staging liver ultrasound (LUS) and bone scan (BS) in early stage disease is unclear. We postulate that early stage breast cancer patients do not need routine radiological staging. Methods: We studied 200 patients with a diagnosis of invasive breast carcinoma. 100 with symptomatic breast cancer (SBC) and 100 with screen detected (SD). Patients’ histology, tumour markers (CEA, CA 15.3), hormone receptor status, CXR, LUS and BS results were reviewed. Results: All patients underwent curative surgery for early stage invasive breast cancer. 3 patients had liver metastases diagnosed by LUS. Two of these patients were from the SBC and one from SD (grade ≥2, mean tumour size 2.2 cm). 4 patients had bony metastases diagnosed by BS. Three of these were from the SBC and one from SD (grade ≥2, mean tumour size 3.2 cm.). No patients with low-grade T1 tumours had signs of metastasis on BS or US. Conclusions: The incidence of metastatic disease is very low in newly diagnosed early stage breast carcinoma. Our results suggest that patients with low-grade T1 tumours do not need staging BS or US.

No significant financial relationships to disclose.
Paclitaxel (P), pegylated liposomal doxorubicin (PLD) and trastuzumab as 1st-line chemotherapy (chemo) in HER2/neu-positive (+) metastatic breast cancer (MBC)
Authors: Karabelis A. , Kosmas C. , Mylonakis N. , Tsakonas G. , Evgenidi K. , Kallistratos E. , Sava L. , Nikolopoulou A. , Gassiamis A. , Valavanis C.
Published: March 2020

10663

Background: Addition of trastuzumab (Herceptin, H) to successive neoadjuvant taxane+anthracycline-based chemo in patients (pts) with HER-2 (+) breast cancer significantly increases the pathological complete response (CR) rates. PLD has considerably less cardiotoxicity compared to parent drug. The aim of the study was to evaluate the activity and safety of combining H with PLD and P as 1st-line chemo in HER-2 (+) MBC pts. Methods: Inclusion criteria were: histologically confirmed MBC or relapsed after adjuvant chemo, ≥1 measurable lesion, adequate organ function, ECOG-PS 0–1, left ventricular ejection fraction (LVEF) by MUGA ≥55% (reevaluated after cycles 3 and 6). HER-2 positivity was determined by IHC and confirmed with CISH. Chemo was administered as follows: H 6mg/kg (8mg/kg-1st cycle) infused over 90min, PLD 35mg/m2 over 1hr, and P 175mg/m2 over 3hrs on day 1, with prophylactic G-CSF, recycled every 3 weeks. In responders, H was administered as consolidation (6mg/kg/3wks) until disease progression. Results: From 10/2003–10/2005, 19 female HER-2 positive MBC pts were enrolled. Median age: 68 (range, 42–78). Metastatic sites were: lung 6, liver 1, bone 3, lymph nodes 11, soft tissue 5 [median: 2 (range, 1–4)]. Pts received a median of 6 (range, 1–8) for a total of 102 cycles. PLD was started at 35 mg/m2, but in pts with grade 3 hand-foot syndrome (HFS) dose was reduced by 25% (6 pts), or the drug was omitted for 1 cycle (1 pt). 17 pts completed 3–6 cycles and were evaluable for response, all treated patients were evaluable for toxicity. Response rates (RR) were 71%; CR 41%, PR 30%, SD 29%, with no PD. Two pts rendered operable had pCR. Toxicities were: HFS; grade 4: 1, grade 3: 6 (overall 37%), grade 3–4 neutropenia: 4, grade 3 anemia: 1, grade 3–4 mucositis: 2, and grade 2 alopecia: 19. Neither significant LVEF decline, nor symptomatic cardiac event was observed. It is too early to provide data on response duration, TTP, and OS, and these will be available at the meeting. Conclusions: H+P+PLD as 1st-line chemo in HER-2(+) MBC pts is a very active and well tolerated regimen with no significant morbidity/mortality. HFS was the most relevant toxicity. The study is ongoing.

No significant financial relationships to disclose.
Preliminary results of docetaxel (T) and trastuzumab (H) combination administered every 21 days in metastatic breast cancer (MBC) and HER-2 over-expression patients (P)
Authors: Tusquets I. , Ramos M. , Gil M. , Sánchez-Rovira P. , Mel J. R. , Duque A. , García-Estévez L. , Velasco A.
Published: March 2020

10670

Background: T combined with weekly H confers greater tumor response and survival compared to T monotherapy in P with Her-2 positive MBC. A recent report has demonstrated that H can be administered q3wks. The primary endpoint is to evaluate time to progression (TTP). Sencondary objectives are response rate, overall survival and safety profile. Methods: P cytologically or histologically confirmed of metastatic breast cancer, HER-2 positive (+++ by Herceptest, or FISH positive), age > 18, ECOG PS ≤ 2, and adequate organ function, were included. Prior chemotherapy for MBC or adjuvant anthracycline-based regimen in the previous 6 months was not allowed. Treatment: T 100 mg/m2 iv D1 q3wks for 6 cycles, H 8 mg/kg (cycle 1) and 6 mg/kg (consecutive cycles) iv D1, q3wks. P may receive H monotherapy until PD at the investigator criteria. Results: Over 41 analyzed P, median age was 57 years (29–75); ECOG PS 0–1 95% and ductal carcinoma 88%. Twenty five P received prior chemotherapy. Treatment: 217 cycles of TH (median 6) were administered. After that, 23 P received 189 cycles of H monotherapy (median 5, 1–32). During TH treatment median RDI was 97% for T and 96% for H, and it was 99% during H treatment. Over 33 P for efficacy analysis (2 consent withdrawal, 1 allergic reaction, 1 ongoing and 4 response not confirmed by RECIST criteria), 6 achieved CR and 12 PR, for an ORR of 54.6% (95% CI: 37.6–71.6). Median follow-up time was 11.8 m and median TTP was 8.8 m (95% CI, 1.9–15.6). All P were evaluable for safety. During TH treatment, grade III/IV neutropenia occurred in 16 cycles (7.4 %), 14 of them were febrile neutropenia episodes (6.5%). Other grade III/IV toxicities per cycle were: leucopenia (5.5%), hyperglycemia (2.3%), anorexia (2.3%) and skin (2.3%). During H monotherapy treatment, the only grade III-IV toxicities observed were, skin (1.6%), oedema (1.1%), nail disorders (0.5%) and malaise (4.3%). Six P (14.6%) dropped out due to cardiac toxicity: 5 had LVEF under 50% and one atrial fibrillation. Conclusions: Preliminary results suggest that TH q3wks followed by H as single agent, is an effective regimen for the treatment of P with Her2 positive MBC.

No significant financial relationships to disclose.
Exemestane (Exe) as primary treatment in hormonosensible early breast cancer of the elderly: Preliminary results of a phase II multicenter open Italian study
Authors: Mustacchi G. , Mansutti M. , Barni S. , Cazzaniga M. E. , Farris A. , Ceccherini R. , Sacco C. , Dellach C.
Published: March 2020

10689

Background: In the late 90s two large phase III trials (GRETA & CRC) showed that tamoxifen as sole treatment was a possible alternative to surgery in old women. Two Phase III neoadjuvant trials showed recently that letrozole is superior and anastrozole is not inferior to tamoxifen.A few phase II and a small fase III trials showed interesting results also with the steroidal inactivator exemestane. Methods: We are running a fase II open trial in early breast cancer patients aged over 70 with receptor rich tumors, treated with exemestane 25 mgs/day for 6 months before surgery. Primary endpoints are clinical response, breast conservative surgery (BCS) rate and safety. Results: Of the planned 100 patients we report preliminary results on 50 patients (mean age 81 , range 70–92) evaluable for clinical and mammographic response. 33/50 had a partial response (66%), 2/50 PD on treatment. Clinical basal mean size of tumors was 4.4 cms (4,81 in responders) and 2,67 cms the final in responders patients. Eight patients refused surgery, 12 are too early, 23/30 underwent BCS where 17 of them (74%) were unfit for BCS at basal evaluation. No remarcable exemestane related toxicity was recorded. Conclusions: As expected from published data of phase III trials in metastatic and adjuvant setting, exemestane appears to be very active also in the neoadjuvant setting. Probably there is no more need of large phase III trials in order to consider exemestane in the preoperative setting in rich receptor tumors. In old and frail patients this could also be considered as sole treatment.

[Table: see text]
Patterns of adjuvant hormonal therapy (AHT) usage in early stage breast cancer (ESBC)
Authors: Cobb P. , Schwartzberg L. S. , Kulig K. , Johns A. , Fortner B.
Published: March 2020

10695

Background: Aromatase inhibitors (AIs) are recommended as first line agents or after tamoxifen (T) as extended adjuvant therapy in hormone receptor positive ESBC. Little is known about adherence, adverse events, toxicity, duration of therapy, or change in agents in the community setting. Disparities between actual usage and clinical guideline recommendations could have a significant impact on outcomes. Methods: This retrospective observational study reviewed charts of 200 ESBC patients (pts) receiving AHT from 4 US community oncology clinics. To be eligible, each patient must have completed >1 patient care monitor (PCM) survey, a validated electronic self-report measure that produces indices related to physical symptoms, psychological symptoms, functional status and overall health-related QOL. Baseline symptoms and toxicities prior to initiation of AHT and during and/or after are available on all evaluable patients. Pt charts were identified consecutively in reverse chronological order starting from 3/01/05. Results: Data are available on 42 pts. The mean age of the patients was 63.6 (range 43–86). First line AHT was T in 24 and AI in 18. Of available AIs, 14 pts received anastrozole, 3 letrozole and 1 exemestane. 18 pts continue AHT as per guidelines and 7 completed planned therapy (median duration, 58.8 months). Switching from 1st line AHT to another agent occurred in 13 pts; 10 switched from TAM to an AI, mean duration of TAM 31.0 months and 3 pts to another AI. 8 pts (19%) changed for an adverse event (AE), and 5 changed due to MD/pt preference. AEs included eye problems (2), weight changes (2), GYN complaints (2), vasomotor symptoms (1), muscle/joint aches (2), and increased alkaline phosphatase (1). Of pts receiving 2nd line AHT, 4 had discontinuation for an AE: muscle/joint aches (2), vasomotor symptoms (1), and eye problems (1). Conclusion: Switching of first line AHT is common for reasons of AEs or MD/pt decision. Pts with AEs to AHT often experience additional AEs after exposure to another agent.

[Table: see text]
Gemcitabine and docetaxel for metastatic breast cancer—Further data
Authors: Laufman L. R. , Spiridonidis C. H. , Parker T. , Boury P. , Maggard V. , Miller S.
Published: March 2020

10704

Background: A previous study with weekly gemcitabine and monthly docetaxel at 100 mg/m2 yielded a 79% response rate and a median survival of 24 months. (Laufman, Ann Oncology 2001; 12:1–6). This study was designed to see if the efficacy to toxicity ratio could be improved by decreasing the docetaxel dose to 75 mg/m2. Methods: Gemcitabine and docetaxel were given to 25 patients, all of whom had received prior chemotherapy. Nine had had taxanes, more than 12 months before entry. A maximum of 6 cycles of gemcitabine 800 mg/m2 on days 1, 8 and 15 and docetaxel 75 mg/m2 on day 1 were given every 28 days. Prophylactic antibiotics were given during neutropenia. Growth factors were used for anemia, neutropenia, or for secondary neutropenic prophylaxis. Maintenance therapy consisting of gemcitabine 800 mg/m2 on days 1, 8 and 15 every 28 days was given to 12 patients, 2 of whom also received consolidation radiation. Results: A total of 122 cycles of induction therapy were given, with 14 patients receiving all 6. Dose delivery was 91.9% for docetaxel and 70.2% for gemcitabine. A total of 43 maintenance cycles were given, ranging from 1 to 12 cycles per patient. Dose delivery was 70.6%. Toxicity consisted of myelosuppression and fatigue. Grade 4 neutropenia occurred in 20 patients but was complicated by infection or fever in only 3. Five patients had grade 3 anemia and 4 had grade 3 thrombocytopenia. Other grade 3 toxicities consisted of fatigue in 8 patients, myalgia/arthralgias in 4, mucositis in 1, pneumonia in 1 and diarrhea in 1. Responses defined by RECIST criteria occurred in 12 patients (48%), including 8 of 16 taxane-naïve and 4 of 9 taxane-exposed patients. Conclusion: This regimen is active, and the most common toxicity is asymptomatic neutropenia. Sponsored by Eli Lilly and Aventis.

No significant financial relationships to disclose.
Prevention of febrile neutropenia by prophylactic use of G-CSF with adjuvant TAC based on risk assessment—Single institute study
Authors: Chellama M. K. , Awadhi S. A. , Vyas V. , Nemec J. , Khodary A. , Enezi F. , Delvadiya M. D.
Published: March 2020

10711

Background: TAC confers significant disease free and overall survival benefits vs FAC for patients with node positive breast cancer. However TAC is associated with higher incidence of febrile neutropenia. In our study prophylactic G-CSF was used in patients, who developed grade 4 neutropenia with ANC < 100 or febrile neutropenia to prior cycle of TAC. Methods: Following surgery, patients with operable, 1–9 nodes positive breast cancer, ECOG 0–1, and adequate hematologic and organ function were enrolled on to the study, and were to receive TAC day 1 every 3 weeks for 6 cycles . All patients received prophylactic Ciprofloxacin 500-mg bid from days 5–14 after each cycle of chemotherapy unless prophylactic G-CSF was given. Eighty three patients were enrolled during the period 13–1-04 to 30–12–05. Patients who had received at least 2 cycles of TAC were eligible for evaluation. Patients were given prophylactic G-CSF if they had profound neutropenia (ANC < 100) or febrile neutropenia in prior cycle. Results: At the cut-off date for this analysis 79 patients were evaluable. 68 patients had completed the planned 6 cycles of TAC. Three, 2, 3 and 3 patients completed 2, 3, 4 and 5 cycles respectively. Sixty one patients required prophylactic G-CSF - 21 after febrile neutropenia in prior cycle, 39 after profound neutropenia in prior cycle and 1 received from first cycle itself because of post operative seroma with diabetes mellitus. 23 patients developed febrile neutropenia (29.1%) - 3, 8, and 12 after 3, 2 and 1 cycles respectively. Only two patients (3.2%) who received prophylactic G-CSF developed febrile neutropenia. Full dose of TAC could be maintained in 98.6% cycles. Conclusions: The use of G-CSF prophylaxis based on risk assessment could prevent febrile neutropenia in patients, who had profound neutropenia in prior cycle. Also G-CSF could prevent further febrile neutropenia in patients who had developed the same in prior cycle. The above strategy helped in maintaining the dose intensity of TAC.

No significant financial relationships to disclose.
Phase II pilot trial of imatinib mesylate with weekly docetaxel in metastatic breast cancer
Authors: Barton J. H. , Liggett W. , Mainwaring M. , Hainsworth J. D. , Simons L. , Spigel D. R. , Burris III H. A. , Yardley D. A.
Published: March 2020

10716

Background: Overexpression of platelet derived growth factor receptor (PDGFR) has been associated with breast cancer tumor progression and may serve as a potential target for therapy. Inhibition of PDGFR signaling in tumor stroma represents a novel strategy that has demonstrated enhanced chemotherapy antitumor effects, decreased tumor interstitial fluid pressure as well as increased tumor transcapillary transport. Imatinib mesylate (G) is a potent PDGFR tyrosine kinase antagonist. This phase II pilot study evaluates the feasibility, toxicity, and efficacy of imatinib administered with docetaxel as a strategy to enhance docetaxel’s chemotherapeutic effects in metastatic breast cancer (MBC). Methods: Eligibility requirements: 0–1 prior regimens for MBC, > 6 months from prior adjuvant taxanes, RECIST measurable disease, ECOG PS 0–2, adequate organ function, < G2 neuropathy. Treatment: docetaxel 30 mg/m2 IV weekly 3 of 4 weeks. Imatinib mesylate 600 mg po QD. Pts were evaluated for response every 8 weeks; treatment continued until progression or toxicity. Results: 7 pts have been enrolled to date. Median age is 61, all with ECOG PS 0. 5 pts received prior adjuvant therapy; 2 pts received prior taxanes. 43% received prior hormonal therapy. Only 1 pt was ER+/PR+. Hematologic toxicity was mild, consisting only of G3/4 anemia in 2 pts and G3 thrombocytopenia in 1. No febrile neutropenia was noted. Nonhematologic toxicity was characterized primarily by G3 GI toxicity: 4 pts diarrhea, 3 N, V, 1 anorexia, 1 abdominal pain. This was attributed to imatinib in all but 1 pt, in whom both drugs were implicated. 2 pts were removed from treatment and 3 pts required dose reductions, all due to GI toxicity consisting of N, V, and diarrhea. 3 pts experienced dose interruptions and 2 pts exhibited disease progression. Conclusion: These early preliminary results demonstrate imatinib mesylate, in combination with weekly docetaxel as a strategy to inhibit breast cancer PDGFR signaling, is feasible. GI toxicity with this combination was prominent and warrants dose modifications. Updated toxicity and efficacy data will be presented.

[Table: see text]
Phase II study of pegylated liposomal doxorubicin plus vinorelbine in metastatic breast cancer
Authors: Del Prete S. , Montella L. , Faiola V. , Guarrasi R. , Busto G. , Addeo R.
Published: March 2020

10718

Background: Pegylated liposomal doxorubicin and vinorelbine are active single agents in metastatic breast cancer (MBC) and lack overlapping toxicity. The possibility of combining these two drugs therefore seems attractive. Methods: Twenty-five patients with MBC entered a phase II study of pegylated liposomal doxorubicin 40 mg/m2 intravenously (i.v.) on day 1 plus vinorelbine 25 mg/m2 i.v. on day 1 and vinorelbine 60 mg/m2 oral on day 14, every 4 weeks. A two-staged Simon accrual design was adopted for this phase II trial. Patients were required to have measurable disease, previous chemotherapy with or without an anthracycline-containing regimen, and a normal left ventricular ejection fraction (LVEF). Results: Twenty-one patients with MBC were eligible, assessable for response and toxicity. The overall response rate (on an intent-to-treat basis) was 36% (9 of 25; 95% CI, 20%-54%). One complete response and 8 partial responses were noted. In addition, 11 patients (44%) had stable disease of > 4 months duration, and 5 patients (20 %) had disease progression. Median time to disease progression was 10 months (range, 3–38 months) and median overall survival was 15 months (range, 4 to > 62 months). Neutropenia was the most frequent toxicity (grade 4 in 30% of patients and 19% of cycles), but neutropenic fever was seen in only 3 cases. No septic deaths occurred. Nonhematologic grade 3 side effects included skin toxicity (palmar-plantar erythrodysesthesia syndrome, 8%) and mucositis (14%). Late alopecia was seen in 51% of patients (grade 1 in 39%, and grade 2 in 12%). The median LVEFs were 64% (range, 50%-81%) at baseline and 62% (range, 37%-70%) after treatment. Only one patient presented an LVEF decrease to < 50%; however, no clinical heart failure was noted, and this patient recovered normal values after cessation of therapy. Conclusions: The combination of pegylated liposomal doxorubicin and vinorelbine can be safely administered to patients with anthracycline-pretreated MBC and is active in this population. Final data analysis will be presented.

No significant financial relationships to disclose.
Efficacy and safety of mitoxantrone-based chemotherapy as adjuvant treatment in elderly patients (EP) with node positive and high risk node negative breast cancer (BC)
Authors: Fedele P. , Rizzo P. , Cusmai A. , D’Amico M. , Chetrì M. C.
Published: March 2020

10738

Background: Breast cancer is a very frequent malignancy among EP. Adjuvant chemotherapy improves survival for patients with early breast cancer, but older woman at high risk of recurrence are frequently not offered adjuvant chemotherapy and few data are available on efficacy, compliance and safety of adjuvant chemotherapy when indicated in EP. Objective: the aim of our study was to determine the efficacy, compliance and safety of adjuvant mitoxantone-based chemotherapy (FNC) in high risk BC patients older than 70. Methods and Results: From July 1994 to July 2005 we treated 30 patients >70 years, who had diagnosed with early BC in our institution. The treatment (mitoxantrone 10 mg/m2, 5-Fluorouracil 600 mg/m2, Cyclophosphamide 600 mg/m2, i.v. on day 1 every 3 weeks for 6 cycles) was indicated if patients had no severe comorbidity and a high risk of recurrence. All the patients had undergone mastectomy (56%) or quadrantectomy plus axillary lymphadenectomy (44%). Patients undergoing conservative surgery were scheduled for radiotherapy that was planned immediately after the end of chemotherapy. Study population age ranged from 70–78 years, mean age of 74 years.PS (ECOG) was 0 in 74% of patients, 1 in 26%. Comorbid conditions were detected in 38% of patients (64% hypertension, 8% arythmia, 10% depression syndrome, 14% arthrosis) Main histologic types were invasive ductal carcinoma (87%) and lobular carcinoma (13%). Stage was IIA in 20%, IIB in 37%, IIIA in 43%. Grading was 2 in 51%, G3 in 49%.Sixty-seven percent of tumors were ER+ PGR+, 20% were ER- PGR-, 8% ER-PGR+, 5% ER+ PGR-. Seventy-five percent of patients received adjuvant endocrine therapy, after the end of chemotherapy. Toxicity was very manageable with grade 3–4 haematological toxicity in 1 patient, nausea and vomiting appeared as grade 0 and 1 severity in 10%, alopecia was extremely mild and appeared as grade 0 and 1 in 12%. Only 1 patient disrupted treatment because of toxicity. The overall and relapse free survival rates were 70% and 73% at the 60-month follow up, respectively. Conclusion: FNC is an effective and well-tolerated combination regimen suitable as adjuvant chemotherapy for high risk breast cancer EP.

No significant financial relationships to disclose.
Trastuzumab in combination with bevacizumab in advanced breast cancer patient resistant to chemotherapy
Authors: Ordonez J. , Gomez Martin C. , Cortes-Funes H.
Published: March 2020

10762

Background: HER2 positive is associated with up-regulation of VEGF in human breast cancer cells. Superior efficacy was observed if anti-HER2 antibody (trastuzumab) (TZB) is given with anti-VEGF antibody (bevacizumab) (BVB) in xenografs models (Konecny G., 2004). In one phase I study with 9 patients (pt), the combination TZB+BVB was well tolerated without important toxicity, achieving 1 complete response and 4 partial responses (Pegram M, 2005). Methods and Result: We report a clinical case of a 48 years old woman with an advanced resistant breast cancer diagnosed in 1995 and treated with radical surgery for a invasive ductal carcinoma pT2N1M0 HHRR - and c-erbB2 positive (+++). She received adjuvant CMF for 6 cycles and local radiotherapy (XRT). In 2000, lung and liver metastases (mts) with increased CA 15.3 serum levels and was treated with paclitaxel + TZB achieving complete response. Maintenance with TZB was given for one additional year. In 2002, bone and brain mts with increase of CA 15.3 and was treated with vinorelbine + TZB with whole brain irradiation. On March 2005, bone and liver progression was treated with capecitabine + TZB and pelvic XRT with control of the mts. On August, pt developed rapid progression of liver mts with intensive abdominal pain requiring high doses of morphine; progressive jaundice (total bilirubin: 24.4 mg/dl) and low performance status. The level of CA 15.3 was 626 U/ml. We decide treatment with TZB + BVB in a biweekly schedule for 6 consecutive weeks. Whole liver XRT was given in two weeks (15.5Gy). The treatment was well tolerated and the pt improves immediately her clinical situation. Levels of CA 15.3 dropped to 161 U/ml and bilirubin to 4.87 mg/dl. The pt continues the treatment in ambulatory regiment for 7 additional weeks. She had a pathological hip fracture at home and was admitted to the Hospital developing an acute lung tromboembolism dying suddenly. Liver metastases still in clinical and biochemical response. Conclusions: The combination of TZB with BVB could be an effective alternative treatment for pt with advanced and resistant breast cancer, erbB2 positive, and need to be explored in clinical trials.

No significant financial relationships to disclose.
Gene expression profiling of circulating tumor cells from breast cancer patients
Authors: Magbanua M. M. , Lang J. E. , Scott J. , Crothers J. R. , Federman S. , Haqq C. , Park J.
Published: March 2020

10769

Background: Levels of circulating tumor cells (CTC) have prognostic and predictive significance in metastatic breast cancer. However, since CTCs are extremely rare, little is known about the actual phenotype of these cells. In order to characterize these cells, we performed cDNA microarray analyses of CTC isolated from peripheral blood (PB) of breast cancer patients. Methods: CTCs were directly isolated via immunomagnetic enrichment (IE) followed by fluorescence activated cell sorting (FACS). Total RNA was then subjected to two rounds of linear amplification and hybridized to cDNA microarrays (∼40,000 cDNAs). Validation studies used spiked BT474 cells. Clinical studies used PB (10–20 ml) from patients with metastatic breast cancer. Results: Rare spiked tumor cells (e.g., 320 cells in 10 mL PB) were efficiently recovered by IE/FACS (50% yield). Expression profiles of recovered cells, both by TaqMan of a 37 gene panel as well as by global gene expression analysis, matched that of BT474 cells in culture. In contrast, these profiles were clearly distinct from that of normal PB, ruling out significant contamination from blood elements. In clinical studies, IE/FACS isolated small numbers of CTCs (10–1000 cells). Expression profiles of CTCs were compared to that of normal blood, primary breast tumors, and normal epithelial samples. Unsupervised hierarchical clustering revealed that CTC profiles were readily distinguished from that of normal blood and normal epithelium; and further analysis revealed that CTC cluster with a subset of primary breast tumors, particularly the basal-like phenotype. Candidate genes associated with the CTC phenotype were also identified. Conclusions: We have developed and validated a method to isolate rare CTCs and profile them via cDNA microarray analysis. In addition, our gene expression analyses of CTC further provide evidence to the malignant nature of these cells. Further expression profiling of CTC may yield insights into their phenotype, pathophysiology and potential as biomarkers.

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What is the yield of regional lymph node dissection following sentinel lymph node involvement in patients with breast cancer?
Authors: Ortega M. , Ruiz-Echarri M. , Prats E. , Lastra R. , Aguirre E. , Lambea J. , Milastre E. , Mayordomo J. , Razola P. , Tres A. , Banzo J.
Published: March 2020

10782

Background: Sentinel lymph node is a minimally invasive and accurate staging procedure for patients with invasive breast cancer. Histological SLN involvement with cancer cells requires regional lymph node dissection. Aim: To verify if subgroups of patients with sentinel lymph node involvement in which the risk of histological involvement of additional regional lymph nodes is minimal can be identified. Methods: Ninety six consecutive patients with invasive breast cancer and tumour size less than two centimeters by mammography, had lymphoscintigraphy with colloidal 99Tc and radioisotope-guided sentinel lymph node biopsy in the University Hospital of Zaragoza from 1999 to 2005.Pathological assessment included serial sections of the sentinel lymph node with inmunohistochemistry for cytokeratins in selected cases.39 patients had histological involvement and are presented in this analysis. Results: All 39 patients were females. Median tumour size was 20 mm (range 5–52) Median number of resected sentinel lymph node was 2 (range 1–5) Median number of involved sentinel lymph node was 1 (range 1–4) Regional lymph node dissection was performed in all patients (Axillary dissection in 31; internal mammary dissection in 1, both in 7). Median number of nodes was 13 (range 2–34) At least 1 additional involved lymph node was found in 19 patients (48%) We have correlated patient age, menopausal status, pathological tumour size, histological grade, estrogen receptors, progesterone receptors and Her2 with the risk of histological lymph node involvement in regional lymph node dissection. Conclusions: Tumour size was significantly associated to such risk:

No significant financial relationships to disclose.