bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjuvant CAF versus AC followed by paclitaxel for operable breast cancer with 4 or more involved axillary lymph nodes: Retrospective analysis
Authors: Ahn J. , Kim S. , Son B. , Ahn S. , Kim W.
Published: March 2020

10610

Background: Recently, adjuvant AC followed by paclitaxel has improved disease-free survival (DFS) or overall survival (OS) of node-positive breast cancer. Although adjuvant TAC, as compared with FAC, significantly improves DFS and OS rate in node-positive breast cancer, AC→T has not been yet compared with FAC. Since 2001, we discussed the options of adjuvant CAF versus AC→T with patients who had 4 or more positive axillary nodes. We evaluated the efficacies of adjuvant CAF and AC→T, retrospectively. Methods: Between September 2001 and July 2004, a total of 1,394 patients underwent surgery and received adjuvant chemotherapy. Among them, 253 (18.1%) patients had 4 or more than axillary nodes and received either six cycles of CAF (n = 116) or 4 cycles of AC→T) (n = 137). The medical records and pathologic data of these patients were reviewed, retrospectively. Results: Median age of all patients was 46 years (range, 22∼76 years). The two groups were well balanced in terms of demographic and tumor characteristics. With a median follow-up period of 24 months (range, 6∼90 months), 49 (19.4%) patients had disease recurrence including 27 (23.3%) in CAF group and 22 (16.1%) in AC→T group (p = 0.155). The 3 year-DFS rate was 68.3% in CAF group and 71.1% in AC→T group (p = 0.9366), and the estimated 3-year OS rate was 90.3% and 92.3%, respectively (p = 0.8237). There was no significant difference in 3-year DFS rate according to hormone-receptor status. Febrile neutropenia occurred in 11 (9.6%) patients in CAF group and 7 (5.1%) patients in AC→T group (p = 0.222). Conclusion: Our data suggest that there is no significant difference in DFS or OS rates between six cycles of CAF and 4 cycles of AC followed by 4 cycles of paclitaxel as adjuvant chemotherapy in patients with 4 or more than involved axillary nodes. However, long-term follow-up period and prospective studies are needed to define better regimen.

No significant financial relationships to disclose.
Oral adjuvant treatment choices and local recurrence risk in early stage breast cancer
Authors: Russo S. A. , Akbari M. , Grann V. R. , Jacobson J. S. , Chen C.
Published: March 2020

10625

Background: Among women (W) with early-stage breast cancer (BC) treated with lumpectomy and radiation therapy (RT), those who also receive oral adjuvant therapy (OAT) have a lower risk of local recurrence (LR). The purpose of this study was to evaluate the associations of age (A), race/ethnicity (RE), education (E), socioeconomic status (SS), LR rate, and knowledge about potential side effects (SE) with W’s willingness to receive OAT. Methods: Between 6/05 and 9/05, we asked W with (+) and without (−) BC to participate in an IRB-approved survey. The survey questionnaire presented W with clinical vignettes including information about RT ± 5 years of OAT and the LR and SE associated with treatment options. It then asked W to choose between the treatment options and to rate them, using a time trade-off method, given LR and SE. Results: The distribution of the 161 respondents (55 (+)BC and 106 (−)BC) by A, RE, E, SS is shown in the table below. A and RE were associated with a W’s choice of combined modality treatment (CMT) consisting of RT and OAT, to decrease the risk of LR (p < 0.009 and p < 0.056). Stratified analysis showed an association between CMT and E (p < 0.006) in W (+)BC; A (p < 0.04) and SS (p < 0.04) were associated with CMT choice when SE were described. In W (−) BC, RE (p < 0.02) and SS (p < 0.04) were associated with CMT choice when SE were described. Compared to W who had used oral contraceptive agents (OCA), women who did not use OCA were 45% less likely to trade time to decrease their risk of LR by taking OAT when told about similar SE between OCA and OAT (OR = 0.55, 95% CI 0.28, 1.09), but this association was not statistically significant. Conclusions: W of various A, RE, E and SS who were given information about treatment choices with LR rates chose therapies that gave them the best chance of disease-free survival. For W (+) BC history, level of E significantly influenced the choice to proceed with CMT. A, RE and SS influenced CMT choice when SE were described. W who had used OCA in the past may have been less concerned than others about potential side effects of OAT.

[Table: see text]

No significant financial relationships to disclose.
Factors influencing the switch from Tamoxifen (TAM) to Aromatase Inhibitors (AIs) as adjuvant therapy in early breast cancer (EBC) patients (pts). Results from the NORA study
Authors: Pronzato P. , Cazzaniga M. E. , Mustacchi G. , De Matteis A. , Di Costanzo F. , Verusio C. , Marzano N. , Rulli E. , Floriani I.
Published: March 2020

10633

Background: Results from recent trials indicate that AIs as adjuvant treatment, either as up-front therapy or sequencing after TAM, can improve the clinical outcome of EBC pts. It is therefore important to assess the prevalence of the AI use in adjuvant setting and the reasons associated to the choice of this treatment. PATIENTS AND Methods: The NORA trial is an observational study, aimed at investigating adjuvant treatment modalities, that consecutively enrolled 3515 EBC pts, according to the following criteria: 10 pts each year starting from 2000 (retrospective cohort) and 20 pts starting from the beginning of 2003 or the date of ethical approval, if subsequent (prospective cohort). Using data from NORA, we focused on the subgroup of pts who switched from TAM to AIs in order to determine which factors are more likely to be associated with the probability of switching. Multivariate analysis was conducted using the Cox’s regression model. Results: Out of 2075 pts who started TAM, 329 (15.9%) switched to AIs. They had a median age of 63.1 yrs, 147 (45.9%) were N+, 190 (57.8%) received chemotherapy, 179 (54.6%) were T1, 248 (77.5%) were ER+/PgR+. Switch from TAM to AIs was influenced by N+ status, previous chemotherapy and age, whereas no effect was observed for T size or HR status. Previous chemotherapy increases the probability of switching by 27% (95% CI -4% to +70%, p = 0.10), each age decade increase by 35% (95% CI +21% to +52%, p < 0.0001), N+ status by 16% (95% CI +1% to 34%, p = 0.03). Conclusion: As expected, high risk N+ pts have higher probabilities to be switched in comparison to other groups, probably due to the encouraging results of AIs trials. In previously treated or older age pts, TAM side effects could have determined the switch.

No significant financial relationships to disclose.
Analysis of skeletal morbidity in breast cancer (BC) patients treated with zoledronic acid (Zol) or placebo: Time to first pathologic fracture
Authors: Sauter N. , Minami H. , Kohno N. , Aogi K. , Takashima S.
Published: March 2020

10639

Background: We have previously reported that Zol significantly delayed time to first skeletal-related event (SRE) compared with placebo in BC patients with bone metastases in a multicenter randomized trial conducted in Japan. Patients with bone metastases from BC suffer from a range of skeletal complications, including pathologic fractures that can dramatically decrease mobility and adversely affect patient autonomy and quality of life. Methods: 228 women with bone metastases were randomized to 4 mg Zol (n = 114) or placebo (n = 114) every 4 weeks for 1 year. Time to first skeletal event was estimated using the Kaplan-Meier method for all individual types of event. Median time to individual skeletal events was not reached in either treatment group; therefore, data are presented as the incidence at 1 year, and the log-rank P value is from the Kaplan-Meier estimate of time to first event. Results: Median time to first SRE (including hypercalcemia) was not reached in the Zol group versus 360 days in the placebo group (P = .002). Time to first pathologic fracture (P = .022), spinal cord compression (P = .022), need for radiation therapy to palliate bone pain (P = .054), and hypercalcemia (P = .040) were all reduced in the Zol group compared with the placebo group. The incidence of each of these events at 1 year is shown in the table . Cox regression analysis (adjusting for stratification factors) also showed that treatment with Zol significantly reduced the risk of pathologic fractures by 39% compared with placebo (hazard ratio = 0.61; P = .041). Conclusions: This prospective analysis of time to first skeletal event demonstrates that treatment of BC patients with Zol significantly delays the onset and reduces the risk of skeletal complications, including pathologic fractures, which may help preserve independence and quality of life.

[Table: see text]

[Table: see text]
Phase II study of weekly nanoparticle paclitaxel (ABI-007), carboplatin and trastuzumab as first-line therapy of HER2-positive metastatic breast cancer
Authors: Seidman A. D. , Danso M. , Bach A. , Smith M. , Liu M. , Dickler M. , Robson M. , Moynahan M. E. , Lake D. , Hudis C. A.
Published: March 2020

10650

Background: The combination of carboplatin (C), paclitaxel (P) and trastuzumab (T) is active in HER2+ metastatic breast cancer (MBC) (Robert N et al. Proc ASCO 2003), and safer with weekly administration of all 3 agents (Perez E et al. Proc ASCO 2004). The superiority of nanoparticle paclitaxel (Abraxane, AB) over Cremophor-based paclitaxel (Gradishar W et al. JCO 2005), and the efficacy and safety of weekly AB in MBC (Blum J et al. Proc ASCO 2005) motivated us to conduct this study. Materials/Methods: To date 10 of 50 planned patients (pts) with measurable, HER2+ MBC have entered. After we established the safety of AB at 75 mg/m2 on days 1, 8, and 15 every 28 days (n = 4 pts), all subsequent pts received AB at 100 mg/m2. C was dosed at AUC = 2 on the same schedule, and T was weekly at 2 mg/kg without interruption, after a 4 mg/kg load. Initially, no prophylactic anti-allergy medication was given. Treatment is until disease progression (PD) or prohibitive toxicity. Pts without PD at 6 months may opt to continue T alone. Median age: 42 yrs (29–66), ECOG PS 0/1 (70/30%); 6 pts had prior adjuvant chemotherapy; 1 with anthracycline (A) and 4 with A + taxane (> 1 yr prior). Results: 68 cycles have been delivered to date (median: 8, range 1–9). Dose reductions of AB and C have been necessary in 4 pts (to 80 mg/m2 and AUC of 1.5 weekly), with delays in 4 pts. 3 pts had hypersensitivity reactions (HSR) to C and continued protocol therapy without C (n = 2) or with C and the addition of anti-HSR premeds (n = 1). Grade ¾ toxicities include neutropenia (44/11%) with 1 episode of febrile neutropenia. Grade ¾ anemia or thrombocytopenia has not occurred. Grade ¾ non-hematologic toxicity has been rare: 1 instance of grade 3 neuropathy (2 pts with grade 2). 7 partial responses have been observed in the first 9 evaluable pts (78%, 95% CI 44–93%), in liver, lung, bone and soft tissue sites, including 4 pts with prior adjuvant taxane. The median time to PD is not reached at 9.9+ months (7.3–9.9+). Accrual continues as the trial expands to additional study sites. Conclusions: The weekly administration of AB, C, and T demonstrates promising preliminary efficacy as 1st-line treatment for HER2+ MBC. With the exception of HSRs due to weekly C, a very favorable toxicity profile is observed.

[Table: see text]
Internet use is associated with utilization of genetic counseling for BRCA 1/2 mutations in women with a family history of breast or ovarian cancer
Authors: Armstrong K. , Gray S. , Domchek S.
Published: March 2020

10654

Background: Women obtain breast cancer risk information from a variety of sources including mass media, the internet and personal and professional sources. Little is know about how internet use for health information influences choices about breast cancer risk evaluation and decision making. Methods: Case control study of 408 women with a family history of breast or ovarian cancer, of whom 217 underwent genetic counseling for BRCA 1/2 testing (cases) and 191 women who did not (controls). Participants received primary care within a large health system in greater Philadelphia, PA. Results: Women with a family history of breast or ovarian cancer who reported frequent use of the internet for health information (>1–2 times a month) were significantly more likely to undergo genetic counseling for BRCA 1/2 testing than women that rarely used the internet to obtain health information (<2 times a year) (odds ratio 2.6; 95% CI 1.7–4.0). This association persisted after adjustment for age, race, education and Gail risk (adjusted odds ratio 2.1; 95% CI 1.05–4.2) Conclusions: Frequent use of the internet for health care information is associated with higher use of genetic counseling for BRCA 1/2 mutations in women with a family history of breast or ovarian cancer. The association can not be explained by differences in education, cancer risk, age or race. A possible hypothesis for this association is that internet use exposes women to more information about genetic testing, BRCA testing opportunities and the experiences of other women who have utilized BRCA counseling services.

No significant financial relationships to disclose.
Correlation of dynamic infrared imaging with radiologic and pathologic response for patients treated with primary systemic therapy for locally advanced breast cancer
Authors: Fanning S. R. , Short S. , Coleman K. , Andresen S. , Budd G. T. , Moore H. , Rim A. , Crowe J. , Weng D. E.
Published: March 2020

10696

Background: Assessment of response to therapy for locally advanced breast cancer includes serial assessments of physical exam, radiologic imaging, or repeated biopsies. Expense, subjective assessment, and patient risk make these methods impractical. Dynamic infrared imaging (DIRI) utilizes a quantum well infrared photon (QWIP) sensor with software to analyze the emission patterns over time. DIRI can detect biological temperature gradients with sensitivity of 0.009ºC. Tumor-induced local tissue nitric oxide production can increase local capillary blood flow. Anti-tumor therapies have been shown to result in decreased peri-tumoral capillary blood flow. These changes in temperature, detected by serial DIRI imaging, may provide a low cost, non-invasive, easily reproducible objective tool for real-time clinical assessment. Methods: In this prospective pilot study, we are evaluating patients with locally advanced breast cancer using serial DIRI. Primary endpoints include: sensitivity, specificity, PPV, and NPV of DIRI in comparison to pathologic response, concordance of DIRI to physical exam, and concordance of DIRI to standard radiographic evaluation at initial diagnosis and prior to surgery. DIRI results are reported as quantification of changes in the 0.2Hz modulation of temperature over the breast during the course of treatment and measurement of area of average temperature in a region of interest compared between breasts. One hundred patients will be enrolled in this trial. Results: Sixteen patients have been enrolled. Six have proceeded to surgery. All but one patient exhibited evidence of tumor response by physical exam. These findings correlated with response when comparing initial to pre-surgical MRI. In all responding patients, DIRI results revealed a decrease in the number of regions over the breast in which the 0.2Hz frequency dominated. Similarly, DIRI evaluation according to area of average temperature in the region of interest compared between breasts was concordant in patients with response to therapy. Conclusions: Assessment of response by physical exam, MRI, and DIRI were consistent. Preliminary data reveals that serial DIRI imaging can be an effective adjunctive tool.

No significant financial relationships to disclose.
Randomized phase II trial of two different schedules of carboplatin (C) and paclitaxel (P) + trastuzumab (T) as first line treatment for metastatic breast cancer (MBC)
Authors: Tauer K. , Schwartzberg L. S. , Epperson A. , Fortner B. V.
Published: March 2020

10697

Background: Platinum compounds given with taxanes have emerged as an active combination for the treatment of MBC. However, optimal scheduling of these drugs is unknown. While evidence suggests weekly P may be superior to Q 3 wks, conflicting data exists for weekly vs. Q 3–4 wk C. Methods: Eligible patients (pts) had no prior chemotherapy for Stage IV disease and no prior exposure to platinum agents. Pts were stratified by HER2 status and randomized to receive either C, AUC 2, day 1,8,15 (C1 arm) + P 80 mg/m2 day 1,8,15 or C, AUC 6 day 1 (C4 arm) + P 80 mg/m2 day 1, 8, 15 in a 28 day cycle. HER2+ pts received T weekly at 2mg/kg after a loading dose of 4 mg/kg. The primary endpoint, overall response rate (ORR), was evaluated after every 2 cycles of therapy. Results: To date, 35 patients have been enrolled (19 HER2+). 31 are evaluable for toxicity and 22 for response. The median age is 52 (range 25–76), 17 had prior adjuvant therapy, median number of sites of disease was 2. Partial responses were noted in 4/10 in C4 arm and 7/12 in C1 arm for an ORR of 50%. The ORR for Her2+ pts to CP+T was 64%. 8/16 (50%) pts on the C4 arm and 2/15 (13.3%) pts on the C1 arm had grade 3/4 toxicity, predominantly hematological. Dose reductions occurred in 3 pts on C4 arm and 3 pts on C1 arm. Conclusions: Carboplatin and paclitaxel (± trastuzumab) is an active regimen when C is given in either weekly or Q 4 wk schedules. Hematologic toxicity is significantly less when C and P are both given weekly, and thus should become the preferred schedule in MBC.

No significant financial relationships to disclose.
Experience with breast cancer in a single oncology clinic in Nairobi
Authors: Othieno-Abinya N. A. , Abwao H. O. , Bird P. , Baraza R. , Byakika B. , Kodwavwalla Y.
Published: March 2020

10714

Background: Combinations of anthracyclines and cyclophosphamide ± 5-FU are widely used in treatment of breast cancer (BC) in the adjuvant setting. Addition of taxanes is beneficial. For Her2-positive tumours addition of herceptin may improve relapse-free survival in the adjuvant setting, and prolongs survival in metastatic setting. We routinely use doxorubicin and cyclophosphamide (AC) x 6 courses for standard risk disease and give the same x 4 followed by docetaxel ± herceptin x 4 for those with ≥ 10 positive axillary nodes. We also use AC as first line for endocrine nonresponsive metastatic BC. Methods: A total of 173 BC patients seen in our clinic between January 1997 and May 2005, 83 were given chemotherapy both in the adjuvant and metastatic settings. Results: Of 83 patients, 81 were female and 2 males, age range 24–71, median 45 years. Seventy-eight cases were ductal carcinoma, not otherwise stated, 1 colloid, 1 anaplastic, 1 adenosarcomatoid, 2 medullary. Fifty-six were post resection and 27 metastatic. Thirty eight sites of metastasis or spread were evaluable. These were skeletal 10 (26.3%), liver 7 (18.4%), chest wall 6 (15.9%), lungs and pleura 9 (23.7%), brain 4 (10.5%) and supraclavicular nodes 2 (5.3%). Her2 expression by immunohistochemistry in 20 cases was - 3+ in 7 (35%), 2+ in 3 (15%) and ≤ 1+ in 10 (50%). Out of 40 cases, 15 (37.5%) were endocrine responsive, 17 (42.5%) nonresponsive and 8 (20%) indeterminate. Twenty seven patients treated before January 2004 were recorded dead after survival ranging between 8 and 96 months, median 36 months. Only 3 patients with resected BC were recorded dead as opposed to 24 with MBC at diagnosis. Two of the deaths in the adjuvant setting were in patients with ≥ 10 nodes positive and both had the brain as the only site of metastasis. There was no significant correlation between nodal status and follow-up duration (P = 0.43), hormone receptor status and survival (P = 0.20), and Her2-expression and survival (P = 0.23). Conclusions: This material shows a low frequency of ER positivity and higher mortality particularly from brain metastasis than most Western series. It does however show a similarity to recent reports of breast cancer in African-American women.

No significant financial relationships to disclose.
High efficacy and low toxicity of the combination of vinorelbine and capecitabine as second line treatment in metastatic breast cancer previously treated with taxanes and/or anthracyclines
Authors: Orphanos G. , Alexopoulos A. , Ioannidis G. , Kandylis C. , Ardavanis A. , Stavrakakis J. , Rigatos G.
Published: March 2020

10719

Background: Capecitabine and Vinorelbine have shown considerable activity given as single agent or in combination with other drugs. The aim of this single institution ph.II study is to evaluate the response to the combination of Capecitabine and Vinorelbine given as second line treatment in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines. Methods: The regimen consists of Capecitabine 2000 mg/m2 D1-D14 and Vinorelbine 20 mg/m2 D1,D8 q 3 weeks for six cycles. Evaluation of response was accomplished with CT scan after the third and sixth cycle. Patients with disease progression after cycle 3 are taken off protocol. Patients with gr 2/3 granulocytopenia are given G-CSF for all subsequent cycles and there is a 20% dose reduction in both drugs for patients with gr 4 granulocytopenia. Results: 30 pts have been enrolled so far; according to statistical planning the total number of accrued pts should reach 63. Median age 55 yrs (30–76), median ECOG PS 1 (0–2), pre/postmenopausal 6/24. Number of metastatic sites: 1 in 6 pts, 2 in 15 pts, 3 in 6 pts and 4 in 3 pts. A total of 146 cycles was administered. Overall response rate 50% with CR in 2 (6.7%) pts, PR in 13 (43.3%) pts. Stable disease was observed in 4 (13.3%) pts, 8 (26.6%) pts had progressive disease and 3 (10%) were non evaluable. Toxicity: anemia gr 2 in 2 (6.7%) pts and gr 3 in 1 (3.3%) ptn, thrombocytopenia gr2 in 2 (6.7%) pts, granulocytopenia gr 2/3 in 17 (56.7%) pts and gr4 in 1 (3.3%) ptn. Gr 1/2 nausea or vomiting was observed in 5 (16.6%) pts and gr 3/4 in 2 (6.7%) pts. Vinorelbine induced phlebitis in 3 (10%) pts, gr1/2 diarrhea in 3 (10%) and fungal infection of the nail beds in 2 (6.7%) pts. Conclusions: Preleminary results suggest that the Capecitabine and Vinorelbine combination is an active and safe regimen for second line metastatic breast cancer treatment. The study remains open to achieve the planned patient accrual.

No significant financial relationships to disclose.
Differences on breast cancer management and surgical approach in six European breast cancer units
Authors: Celebic A. , Halaska M. , Kosovac O. , Stojiljkovic D. , Milovanovic Z. , Miletic N. , Dzodic R.
Published: March 2020

10737

Background: Paper was aimed to compare differences in pre-operative management, decision on surgery and surgical approach for breast cancer in six European Breast Cancer Units in Italy, France, Czech Republic and Serbia and Montenegro, and to discuss impact of detected differences on outcome of the disease. Methods: The authors of this paper, who have been invited as young visiting/observing/training guests by four prestigious European Breast Cancer Units in Italy and France (National Cancer Institute - Milan, European Institute of Oncology - Milan, Institute Gustave Roussy - Villejuif, Institute Curie - Paris) as fellows of different European and international institutions (EUSOMA, EACR, ESSO, UICC, ESO, FECS, French Government) in the period 2003–2005, tried to detect and compare differences regarding pre-surgical evaluation, decision making and surgical approach for breast cancer as well as to discuss the impact of identified changes on outcome of the disease. The special attention has been directed to inspection of such small details as waiting list for consultation and hospitalisation, way of decision for surgical intervention (individual or oncology meeting/staff), horizontal or oblique incision for mastectomy, duration of hospital stay, sentinel node procedure (blue dye, radioactive tracer or both, one or two-days protocol, imunochistochemistry examinations during frozen section or not), preferred way of breast reconstruction, number of assistants during operation, drainage, preservation of intercostobrachial nerve during axillary surgery, suture, etc. The data were collected according to personal presence in different institutes, observation and asking the questions. Descriptive statistics were used to show the differences among the parameters under comparison. Results: This study which clearly showed a great range of differences, sometimes very significant, in parameters regarding pre-surgical evaluation and surgical treatment of breast cancer. Conclusions: Although being found, and sometimes significant, the observed differences in several parameters regarding pre-operative evaluation and surgical treatment of breast cancer in six European breast cancer units do not have influence to the outcome of the breast cancer.

No significant financial relationships to disclose.
Biological characteristics of oestrogen receptor positive early operable primary breast cancer in the elderly
Authors: Ying M. W. , Green A. R. , Agrawal A. , Paish C. E. , Morgan D. A. , Ellis I. O. , Cheung K. L.
Published: March 2020

10739

Background: Over half of breast cancer are diagnosed at >65 years and increasingly more are diagnosed in the elderly population. However little is known about their biological characteristics, which may be important in therapeutic strategies such as selecting endocrine agents as primary, neoadjuvant or adjuvant therapy. We report the pattern of oestrogen receptor (ER), progesterone receptor (PgR) and HER2 status in a cohort of elderly patients with primary breast cancer (PBC). Methods: All elderly (> 70 years) patients, who had ER positive early operable PBC (< 5 cm) and who refused or were unfit for surgery, were treated with primary endocrine therapy. Standard immunohistochemical staining was performed on core biopsy tumour tissuefor ER, PgR and HER2. Positivity for ER and PgR was defined by H-score ≥ 50, and HER2 positivity was defined as 3+. Results: A total of 86 such patients were treated over a two-year period and the biological characteristics of their tumours were as follows (see Table ). Conclusions: Within the group of ER positive patients, approximately half of the tumours also expressed PgR. The total number of HER2 positive tumours was small although the majority of these were PgR negative. Clinical follow-up is ongoing to elucidate the relationship between endocrine sensitivity and these biological characteristics.

[Table: see text]

[Table: see text]
Cowden Syndrome as an indication for bilateral prophyllactic mastectomy: A series of two cases
Authors: Loewen M. , Ashikari A. , Kelemen P. , Salzberg A. , Savino J. , Ashikari R.
Published: March 2020

10761

Background: Multiple hamartoma syndrome, or Cowden Syndrome, is an autosomal dominant disorder which predisposes toward neoplasms in the thyroid, colon, and breast. Chemoprevention in women with a genetic predisposition toward breast cancer has not yet been shown to be beneficial in prospective data. Bilateral prophylactic mastectomy (BMP) has emerged as a viable option for women with suspected genetic predispositions toward breast cancer, with an estimated risk reduction of around 90 percent. Our search of the literature has not detected any case series of BMP in the Cowden Syndrome patients. Methods: We present two women presenting with historical and physical evidence for this Cowden Syndrome with desire to undergoing PBM. Results: Both women successfully underwent subcutaneous bilateral mastectomy with immediate reconstruction. (See table ) They are both alive without evidence of breast cancer to date. Conclusions: Cowden Syndrome can be added to other genetic syndromes with clear predispositions toward breast cancer, and presents an option for prophylactic bilateral mastectomy in women who desire a risk reduction for breast cancer.

[Table: see text]

No significant financial relationships to disclose.
Transplantation for breast cancer: Oncologists beware—a multicenter phase I-II study open to enrollment
Authors: Van Hoef M. E.
Published: March 2020

10763

Introduction: After a surge of autologous transplantation (auto-tx) for breast cancer (brca) in the 90s numbers decreased; however, early results of auto-tx in brca were promising; moreover, a graft versus tumor effect was reported for metastatic brca following ablative allogeneic transplant (allo-tx) (Blood 96;88:15011; JCO 98;16:9862). First results of non-myeloablative allo-tx (NMT) in other diseases suggested reduction of adverse effects. Methods: In 2000 a by donor availability controlled multicenter study of dose dense chemotherapy (ChT) (500/100/500) FEC + G-CSF (×4) at 2 wk intervals, semi-high-dose (3000/250/800) auto-tx (×2) at 4 wk intervals to consolidate or enhance complete response rates and a non-myeloablative (8/120/1050–Bu/Flu/Cy) allo-tx for newly diagnosed metastatic breast cancer was designed; all ChT scheduled within 7 mth; GVHD prophylaxis and treatment; supportive care recommendationw. Feasibility, treatment related mortality, DFS and OS major endpoints. The study was promoted. Results: In 2000 and 2001 no papers on allo-tx for brca were published. Since 2002 there are a hand full of case reports or pilot studies about NMT for advanced brca; ample commentaries emphasize clinical response in advanced disease and recent reports also eradication of micrometastatic bone marrow disease. HD-auto-tx/NMT-allo tx was recently reported for advanced disease. No multicenter studies have been reported. The above study remains open to enrollment. Discussion: The treatment method and timing of treatment does hypothetically reduce health care costs. In order to assess the value compared to standard therapy (6 cycles ChT), treatment and outcome utilities can be assigned and a standard cohort be added. Normal life expectance when alive without disease at five years is used for computation of incremental cost beyond five years. In addition, utilities are assigned for activity in good health during the remaining productive years of life. The economic and societal value will be discussed.

No significant financial relationships to disclose.
Providing information and support on all aspects of breast health and breast cancer in Ireland
Authors: Fitzgibbon N. , Langtry A.
Published: March 2020

10766

In 2001 the Irish Cancer Society launched Action Breast Cancer (ABC) to provide breast cancer information and support. ABC’s services are free, confidential and accessible and include a national helpline, patient education, one-to-one support, health promotion, research, advocacy, and professional support. Over the last five years, we have been continually developing our services to the public, at the heart of which is the Freefone Helpline (1800 30 90 40). The Helpline is staffed by specialist cancer nurses who offer information, support, and appropriate referral for women who are concerned about breast health, women who have been diagnosed with breast cancer, their families and carers, and healthcare professionals. In order to meet the need for clear, concise information, we are continually producing and updating literature and supporting materials. This includes a series of factsheets on all aspect of a breast cancer diagnosis including the different aspects of living with the disease. In January 2005, we launched a programme to address the unique needs of younger women with breast cancer. Services include conferences for younger women, a specialist nurse, and the selection and training of younger Reach to Recovery volunteers. Professional support is also a key element of ABC’s service. Most recently we have developed a workshop for nurses working in oncology to improve communication with breast cancer patients around sexuality. ABC’s annual Breast Cancer Awareness Month campaign takes place in October. A high profile advertising campaign and a nationwide roadshow are just two of the many mediums used to target Irish women in order to make them breast aware for life. Throughout the year, ABC is constantly seeking to raise awareness in communities and workplaces across the country by organising presentations about breast awareness, screening and early detection. Now that we have firmly established ourselves as the leading provider of breast cancer information and support, we have started to significantly develop our advocacy programme, and we are currently working on ensuring that the national breast screening programme will be fully rolled out by the end of 2007. We are also undertaking major nationwide research into the provision, supply and fitting of breast prostheses.

No significant financial relationships to disclose.
Capecitabine (Xeloda) and quality of life (QoL) in patients (pts) with metastatic breast cancer (MBC) relapsing after treatment with anthracycline and taxane containing–therapy
Authors: Grecea Sr. D. , Neamtiu L. , Vasiliniuc C. , Tanasescu R. , Rancea A. , Resiga L. , Galatar M. , Popita V. , Daicoviciu D. , Postescu D. , Ghilezan N.
Published: March 2020

10774

Background: The study was designed to evaluate further the efficacy and safety of capecitabine in patients with MBC previously treated with antracycline and taxane. In addition to response rates and survival times, pts preference for oral therapy and QoL are increasingly important considerations in MBC. Methods: All MBC patients had to have documented progression after antracycline and taxane- containing chemotherapy in neoadjuvant or adjuvant setting, no more than one line for MBC. Treatement comprised 3-week cycles of oral capecitabine 1250 mg/m2 twice- daily for 14 days followed by a 7-day rest period. Results: From December 2002 to November 2005, 35 pts were enrolled. Baseline characteristics of the pts. were: median age 51 years (range 33–73), median ECOG PS 1 (range 0–2) and adequate bone marrow, renal and hepatic functions. Median number of metastatic sites was 2 (range 1–5). The pts were evaluable for response and toxicity and received a total of 162 cycles of chemotherapy. Disease stabilization occurred in 11 pts (31.4%), the overall response was 34.2%, ten pts (28.5%) achieved a partial response, two patients (5.7%) achieved a complete response. Median duration of response was 5 months and median overall survival was 8 months with significant advantage for responding patients. For pts achieving a CR or PR, median survival was 13 months, for SD 10 months and for pts with PD as best response 5 months. The most treatment-related adverse events were grade 1/2 in intensity: grade 3 treatment-related adverse events were hand-foot syndrome (11%), diarrhea (7%), vomiting (5%), and nausea (6%). Pts had a significant, sustained improvement in the following: global health status, role and emotional functioning, social functioning, breast symptoms, arm symptoms and hair loss. Conclusions: This study confirms that capecitabine achieves a high tumor control rate in heavily pretreated MBC pts. Pts had a significant improvement in global health status, with substantial improvements in almost all functional and symptomatic QoL domains. Capecitabine should be considered the reference treatment in this setting based on consistently high efficacy and good tolerability.

No significant financial relationships to disclose.
Primary chemotherapy in breast cancer shows excellent clinical and pathological response with docetaxel and epirubicin
Authors: Marana H. R. , Andrade J. M. , Tiezzi D. G. , Zola F. E. , Carrara H. H. , Reis F. C. , Bighetti S.
Published: March 2020

10779

Background: Primary chemotherapy is becoming the standard of care for locally advanced breast cancer. Recently tested regimens using new drugs have been showing better results than usual anthracycline based treatments. Methods: From April 1998 through April 2004, 104 patients (18 stage IIA; 36 stage IIB; 13 stage IIIA; 33 stage IIIB; 4 stage IV) were included in the trial and received three cycles of docetaxel 75 mg/m2 and epirubicin 50 mg/m2 (q3w). Patients with stable or progressive disease were excluded from the trial, receiving alternative treatment. Those with partial response after three cycles but still not suitable for conservative surgery received up to 3 additional cycles. Following completion of the chemotherapy regimen, tumour response was assessed and appropriate surgery performed. Pathological response was evaluated in excised specimens. Results: According to the UICC criteria for clinical evaluation, 79 pts (76%) had objective regression (14 CR and 65 PR); 21 resulted in stabilised disease and 4 showed progression (24%). There was no toxicity in 62 patients, grade I/II in 4 and grade III/IV in seven patient. Ninity-nine patients became eligible for surgery (95%); 60 underwent conservative surgical treatment (60.6%) and in 39 patients a modified radical surgery was done (39.4%). No axyllary involvement were detected in 22 patients, other 23 had 1–3 positive nodes and 54 had 3 or more positives node in axillary dissection. 338 chemotherapy cycles were given, with an average of previously expected 3.25 cycles per patient. Conclusions: Our study demonstrates a high response rate with primary docetaxel and epirubicin chemotherapy in locally advanced breast cancer and high axillary envolvement group, enabling conservative surgery to take place and carrying no significant toxicity. Survival rate was directly linked to pathological response and complete response was associated to highest rate of survival in the group.

No significant financial relationships to disclose.
Neoplastic meningitis in unknown primary neoplasms
Authors: Loghin M. E. , Groves M. D.
Published: March 2020

11517

Background: Neoplastic meningitis (NM) is diagnosed in 5–8% of patients with solid tumors. Unknown primary cancers (UPC) constitute 1% to 7% of NM cases. There is scattered data addressing NM in the context of UPC. Here we characterize the clinical manifestations, prognostic factors and survival outcomes in patients with NM from UPC. Methods: Through an IRB-approved, retrospective chart-review, spanning 1944–2002, we identified 38 patients with UPC, with NM either the presenting feature or a later manifestation of their systemic cancer. Imaging studies were also reviewed. Results: Median age at UPC diagnosis was 44 (13–72 years); for those patients not presenting with NM, time from UPC diagnosis to NM diagnosis was 10 weeks (range 3–60 weeks). Five patients presented with NM as the first and only manifestation of cancer, 1 presented with NM simultaneously with UPC, and 32 patients presented with UPC, followed by NM. Sixteen of those 32 patients presented with central nervous system (CNS) metastases concomitantly with their UPC diagnosis. The final cancer diagnoses were: melanoma (n=21), adenocarcinoma (n=12), small cell undifferentiated carcinoma (n=2), undifferentiated malignant tumor (n=1), Ewing sarcoma (n=1) and sarcomatoid carcinoma (n=1). The median overall survival after the initial diagnosis of UPC was 54 weeks (range: 6–344 weeks), and the median survival after the diagnosis of NM was 10.7 weeks (range: 2–132 weeks). Thirteen patients had a prolonged survival after the diagnosis of NM (24–132 weeks), 8 with melanoma, 3 with adenocarcinoma, 2 with small cell cancer. Six of the 8 melanoma patients with prolonged survival presented with only CNS disease, and none developed other metastatic sites during the course of their disease. Conclusions: Patients with NM and UPC have a poor prognosis. The most commonly identified primary tumors in patients with NM and UPC are melanoma and adenocarcinoma. UPC presenting as NM, and found to be melanoma limited to the CNS and or meninges, carries a better prognosis than other UPCs with NM where systemic tumor burden is identified. This may aid in the systemic diagnostic evaluation and treatment of such patients.

No significant financial relationships to disclose.
Frameless Cyberknife radiosurgery for metastatic and primary brain tumors
Authors: Wong E. T. , Lu X. , Devulapalli J. , Mahadevan A.
Published: March 2020

11527

Background: Cyberknife delivers image-guided stereotactic radiation to intracranial and extracranial skull base tumors without a frame. This frameless feature makes Cyberknife a completely non-invasive procedure and allows non-surgical neuro-oncology personnel to treat patients with tumors in the neuraxis. Methods: Patients with intracranial tumors were selected from our Brain Tumor Clinic if they were not surgical candidates or had residual tumors after neurosurgery. The decision for Cyberknife radiosurgery was made after careful review of all available treatment options in our multidisciplinary brain tumor conference based on patients’ history and neurologic findings, neuroimaging data, and pathology. All patients signed informed consent prior to fusion head MRI and CT scanning. They were pre-medicated with 4 mg of dexamethasone and 500 mg of levetiracetam twice daily. All dose plans were calculated based on CT images acquired from 1.25-mm slices with an inverse planning technique. Dynamic tracking software monitored patient movements and adjusted the robotic arm accordingly, compensating for patient motion up to 10 mm in translation and 5 degree in rotation. Results: Nine subjects with 15 treatment targets, including 4 meningiomas, 1 high-grade glioma, 1 plasmacytoma, and 3 melanomas, were treated with single-fraction or 5 fractions of Cyberknife radiosurgery. No acute toxicity was seen during or within 24 hours of treatment. One subject developed subacute onset of cerebral edema 2 weeks after the procedure but his symptoms were quickly reversed with dexamethasone. Conclusions: Cyberknife radiosurgery is a well-tolerated procedure for intracranial and extracranial tumors in the skull base. Neuro-oncologist, with the appropriate training, could perform Cyberknife radiation planning with radiation oncologists and physicists.

No significant financial relationships to disclose.
Phase I, pharmacokinetic (PK), pharmacodynamic study of paricalcitol [19-nor-1 alpha, 25-(OH)2 D2] in combination with gemcitabine [2’,2’ difluorodeoxycytidine] in patients with advanced malignancies
Authors: Trump D. , Javle M. , Muindi J. , Pendyala L. , Yu W. , Ramnath N. , Ross M. , Fakih M. , Iyer R. , Johnson C.
Published: March 2020

12010

Background: Calcitriol+ gemcitabine (gem) combination results in synergistic anti-tumor effect in preclinical models. Cytidine deaminase (CDD) inactivates gem into 2’,2’-difluorodeoxyuridine (dFdU) and its overexpression may lead to gem resistance. Calcitriol decreases CDD activity in peripheral blood mononuclear cells (PBM). Paricalcitol is cytotoxic in vitro and synergistic with several chemotherapeutic agents, including gem. We are conducting a phase I study of paricalcitol + fixed-dose gem. Objectives: The primary aim is to determine maximum tolerated dose (MTD) of the combination in patients (pts) with advanced cancer. Secondary aims are to evaluate toxicity, the effect of paricalcitol on gem PK, CDD activity in PBM and clinical outcome. Methods: Each cycle is 4 weeks: Gem 800 mg/m2 (over 80 min) weekly × 3, starting day 1; paricalcitol weekly, 24 h prior to gem, starting day 7. Standard 3+3 dose-escalation schema is used. Planned paricalcitol doses are 0.24, 0.72, 1.20, 1.8, 2.4 μg/kg, and 25% increments till MTD. Gem PK and CDD activity (PBM) are studied on days 1 and 8. Paricalcitol PK studies are obtained on day 7. Results: Fourteen pts with the following cancers: pancreatic (n=3), colon (n=3), lung (n=5), esophageal (n=1), bladder (n=1) and unknown primary (n=1) have been enrolled. No dose limiting toxicities have occurred. Median of 2 cycles were delivered (range 1–9). Grade 3 toxicities: anemia (n=3 pts), neutropenia (n=5), thrombocytopenia (n=3), thrombosis (n=2), anorexia (n=1), hypophosphatemia (n=1), dehydration (n=1), syncope (n=1), pneumonia (n=1) and chills (n=1). Grade 4 toxicities: anemia (n=1) and neutropenia (n=1). Hypercalcemia (> grade 1) did not occur. Stable disease occurred in 2 and progressive disease in 3. Conclusions: MTD was not reached at 1.8 μg/kg of paricalcitol with gem 800 mg/m2/week. Dose escalation is ongoing. PK data will be presented at meeting. Supported by NIH grants CA67267 and CA85142.

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Evaluation of tolerability, safety, and pharmacokinetics of INO-1001 plus temozolomide (TMZ) in patients with unresectable stage III/IV melanoma
Authors: Wang C. , Bedikian A. Y. , Kim K. , Papadopoulos N. E. , Hwu W. , Hwu P.
Published: March 2020

12015

Background: TMZ, an orally bioavailable cytotoxic agent with the same active metabolite as DTIC, is a commonly used for treatment (Rx) of metastatic melanoma (MM). It causes methylation of the O6 position of guanine. Unrepaired O6-methylguanine pairs with thymine rather than guanine and activates DNA mismatch repair. Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear protein that functions as DNA damage sensor. PARP inhibitors increase TMZ cytotoxicity by causing interruption of the repair process of N-methylpurines generated by TMZ. INO-1001 (INO), an ultrapotent PARP inhibitor has been tested in combination of TMZ and found to be safe and well tolerated. Here we report the initial results of Phase Ib clinical trial. Methods: Patients (pts) with unresectable stage III/IV MM with no prior Rx with TMZ or DTIC were treated with INO given IV q 12 hours for 10 doses at the starting dose of 100mg/dose. The doses of INO are planned to escalate from 100 to 200mg/dose and then to the maximum dose of 400 mg/dose in successive groups of 3–6 pts. TMZ is taken po within 2 hours of the second dose of INO at the dose of 200mg/m2/day for 5 days. Blood samples are collected for pharmacokinetics study during cycle 1. The Rx cycles are repeated q 4 weeks and tumor responses are evaluated q 8 weeks. Results: 6 pts with median age 63 (range 55–67) years and median PS Zubrod 1 (range 0–2) have been treated. Initially 3 pts were treated with INO at the dose level of 100mg. One pt with a BSA of 2.76 had grade 4 neutropenia and thrombocytopenia with Rx cycle 1. TMZ dose was not adjusted to her ideal body weight. Subsequently, the dose of TMZ was reduced by 25% and the following 2 cycles were tolerated well. 3 more pts were entered at the dose level 1. To date, a total of 8 cycles of Rx have been completed. All except for the cycle mentioned earlier were tolerated well. 3 pts were evaluated for response, 1 pt had objective tumor regression, 1 had stable disease and 1 had tumor progression. The non-hematologic side effects were mild and are mostly related to TMZ. Conclusions: TMZ-INO combination is fairly well tolerated. A complete report will be presented.

No significant financial relationships to disclose.