bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of pregnancy, in the year prior and after treatment for breast carcinoma, on survival and recurrence in women with breast cancer younger than 35 years. GETNA GROUP
Authors: Largillier R. , Savignoni A. , Gligorov J. , Chollet P. , Guillaume M. , Spielmann M. , Luporsi E. , Asselain B. , Coudert B. , Namer M.
Published: March 2020

553

Background: The goal of this study was to assess the effect of pregnancy on the subsequent risk of recurrences after treatment for breast carcinoma, adjusted on established prognostic factors Methods: Between 1990 and 1999, 908 patients aged under 35 years old were treated for a non metastatic and unilateral invasive breast carcinoma in eight french hospitals, members of the GETNA association. The median follow-up period was 87 months. Mean age was 31.4 years old. Estrogen receptor (ER) status, lymph node involvement, tumor size, histological grade and pregnancy were evaluated as potential risk factors for recurrence and death in a multivariate analysis. A modified model was constructed using the four independent variables derived from the previous multivariate Cox model and the annual risk of death and recurrences were studied. Results: Women who gave birth within one year prior to diagnosis (n=105, 11, 8%) were more likely to have axillary node positive (> N1:48%, vs 35%, p=0.009) important tumor size (>T2:75% vs 55%, p=0.0002), and ER negative (54%, vs 42%, p=0.031). In univariate analysis, pregnancy the year before carcinoma diagnosis increased the risk of death, HR=1.5 [1.05–2.20] (p=0.028) and local recurrence, HR=1.71 [1.06–2.76] (p=0.027). In multivariate analysis, only influence on local recurrence is confirmed, HR=1.75 [1.08–2.84] (p=0.006). Patients who experienced a pregnancy after diagnosis and treatment (n=118, 13.4%) did not tend to have better prognosis regarding axillary node positive (> N1:71%, vs 61%, p=0.051), tumour size (> T2:53.4% vs 59.2%, p=0.49), ER negative (ER:44.2% vs 43.6%, p=0.92) and were significantly younger (<30 years old 52.5% vs 28%, p<10−4). The overall survival after five years was 97% for women who experienced a pregnancy and only 80% for those who did not (p< 0.0001). Conclusions: In this large study population, pregnancy was not associated with poorer survival and the healthy mother effect was studied. For the purpose of advising women on the decision to go forward with pregnancy, was studied after the diagnosis and treatment of breast carcinoma, the annual risk of recurrences. Study granted by Sanofi-Aventis. Acknoledgements to OSMO for its operational support.

No significant financial relationships to disclose.
Phase II study of gefitinib in patients with metastatic/recurrent squamous cell carcinoma of the skin
Authors: Glisson B. S. , Kim E. S. , Kies M. S. , Francisco M. , Blumenschein G. R. , Tsao A. S. , Clayman G. L. , Duvic M. , Weber R. S. , Lippman S. M.
Published: March 2020

5531

Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers. Skin squamous cell cancer (SCC) has been increasing in incidence at the rate of 4% to 8% per year since the 1960s, with especially increased rates (up to 10% annually) in recent years. Treatment options for advanced or recurrent skin SCC are extremely limited. Patients (pts) who fail surgery, radiation and/or chemotherapy have a very poor prognosis. Because of the importance of EGFR in tumorigenesis, and its overexpression in squamous cell carcinoma of the skin, it is an interesting target for treatment intervention. Gefitinib, an EGFR tyrosine kinase inhibitor, had a 11% response rate in HNSCC. Because of the possible efficacy, we proposed to study gefitinib in advanced skin SCC. Methods: Pts were required to have pathologically confirmed skin SCC adequate performance status, measurable disease, no prior EGFR therapy, and may have received prior chemotherapy. Pts must not have been amenable for curative intenet therapy with surgery or radiation. Treatment included gefitinib 250mg orally daily for 4 weeks. Results: 18 pts have been enrolled and 17 are evaluable. Median age is 68 years (range 37–84). Median ECOG PS is 1 (range 1–2). 12 pts are men and 5 women. 15 pts are currently evaluable for response. No objective partial responses were observed per WHO criteria. 4 pts (27%) have stable disease. Clinical responses were noted in 2 pts via photographs and clinical inspection. 17 pts are evaluable for toxicity. 2 pts had grade 3 rash and 1 pt had grade 3 keratitis. The most common grade 1–2 toxicities were diarrhea and fatigue. Conclusions: Gefitinib is well tolerated and has modest activity in advanced skin SCC. These pts have very few options for therapy. Data collection for response rate, duration of response and survival is ongoing as several patients are still receiving treatment.

[Table: see text]
Induction chemotherapy + gefitinib followed by concurrent chemotherapy/radiation therapy/gefitinib for patients (pts) with locally advanced squamous carcinoma of the head and neck: A phase I/II trial of the Minnie Pearl Cancer Research Network
Authors: Doss H. H. , Greco F. A. , Meluch A. A. , Gray J. R. , Spigel D. R. , Shipley D. L. , Barton J. H. , Kuzur M. E. , Ramsey S. , Lunin S. D. , Hainsworth J. D.
Published: March 2020

5543

Background: Concurrent chemotherapy/radiation therapy (RT) improves treatment outcome in pts with locally advanced unresectable squamous cancers of the head and neck. We previously reported a 51% 3-year disease-free survival with induction paclitaxel/carboplatin/5-FU followed by concurrent paclitaxel/carboplatin/RT. In this phase II trial, we added gefitinib, an EGFR inhibitor, to a similar chemoradiation regimen. Methods: All pts had squamous carcinoma of the head and neck, with at least one of the following: N1-N3 disease, T3 or T4 primary lesion, nasopharynx primary (except T1N0M0). Additional eligibility: no previous therapy, ECOG PS 0 or 1, adequate bone marrow, kidney, liver function; informed consent. All pts received initial docetaxel 60mg/m2 D1, 22; carboplatin AUC 5.0 D1, 22; 5-FU 200mg/m2, 24-hour CI, D1–43; gefitinib 250mg PO qd, D1–43. Beginning week 8, pts received RT, 1.8Gy single daily dose to total 68.4 Gy, and concurrent docetaxel 20mg/m2 weekly × 6 doses + gefitinib 250mg PO daily. At completion of therapy, pts were reevaluated with CT scans and endoscopy. Results: 45 pts entered this trial between 8/04 and 8/05. Pertinent clinical characteristics: clinical T3/T4, 17; N2/N3, 23. 42 pts (93%) completed induction chemotherapy. 34 pts (76%) have completed combined modality therapy and have been restaged. Response to treatment: 11 CR (32%); 18 PR (53%); 5 stable/progression (15%). After median follow-up 7 months, 9 patients (20%) have developed progressive cancer. Actuarial PFS and OS at 1 year are 68% and 86%, respectively. Grade 3/4 myelosuppression was common, and grade 3/4 mucositis occurred in all pts during combined modality therapy. One pt had a treatment-related death during combined modality therapy. The addition of gefitinib did not substantially increase toxicity. Conclusions: This combined modality regimen was feasible and produced high response rates in pts with locally advanced head and neck cancer. Toxicity was consistent with other effective combined modality regimens for these pts. Further follow-up is needed to better assess the benefit of this approach.

[Table: see text]
Phase I study of the EGFR tyrosine kinase inhibitor erlotinib in combination with docetaxel and radiation in locally advanced squamous cell cancer of the head and neck (SCCHN)
Authors: Savvides P. , Agarwala S. S. , Greskovich J. , Argiris A. , Bokar J. , Cooney M. , Hoppel C. , Stepnick D. W. , Lavertu P. , Remick S.
Published: March 2020

5545

Background: EGFR is highly expressed in SCCHN, representing a promising therapeutic target. Erlotinib (E) is an EGFR tyrosine kinase inhibitor that may potentiate the efficacy of concurrent radiation (RT) and docetaxel (D). We sought to establish the MTD, toxicities and preliminary efficacy of the combination of RT, D and E in patients (pts) with SCCHN. Methods: Patients with previously untreated stage III-IVB SCCHN were enrolled in a phase I dose-escalating study with standard once-daily RT (70.2 Gy, 1.8 Gy/day), weekly D for the duration of RT and daily E for two weeks prior, during and up to two years following RT. 4 dose levels (DL) were evaluated [D (mg/m2)/E (mg): 15/50, 15/100, 20/100, 20/150]. A 3+3 escalation design was followed. Pharmacokinetic studies (PK) were performed. Results: A total of 23 patients were enrolled (6 pts at each DL 1–3, 5 pts at DL4). Primary site: oral cavity (n = 1), pharynx (n = 15) and larynx (n = 7). 20 patients (87%) had stage IV disease. Three dose-limiting toxicities were observed, 1 at each DL (1–3), including a death within 30 days from last treatment (DL1), grade 3 mucositis resulting in holding RT (>5 days) (DL2) and grade 4 mucositis (DL3). No DLT to date on DL4 with 3/5 pts evaluable. In patients enrolled at DL 1–3 (n = 18), post concurrent chemoRT, best response was CR (n = 15), not evaluable (n = 2), death on study (n = 1). 3/3 pts who underwent planned neck dissection had a pathologic CR. 9 patients are currently receiving adjuvant E and 1 has completed the 2-year course. 3 patients have relapsed. Interpatient variability of E peak plasma concentrations measured after the first dose was observed at all dose levels: 458 ± 173 ng/mL (DL1), 686 ± 364 (DL2), 1017 ± 241 (DL3), 833 ± 222 (DL4) (mean ± s.d., n = 6, 6, 6, 2 at DL1–4 respectively). Adjuvant erlotinib plasma concentration data will be presented separately. No significant PK interaction of erlotinib with docetaxel was noted. Conclusions: The combination of daily erlotinib with weekly docetaxel and RT for pts with stage III-IVB SCCHN is feasible and active. A phase II trial is planned. Supported in part by NIH grants nos. CA62502 and M01 RR-000080.

No significant financial relationships to disclose.
The letrozole (L), exemestane (E), and anastrozole (A) pharmacodynamics (LEAP) trial: A direct comparison of bone biochemical measurements between aromatase inhibitors (AIs) in healthy postmenopausal women
Authors: McCloskey E. , Hannon R. , Lakner G. , Clack G. , Miyamoto A. , Eastell R.
Published: March 2020

555

Background: The LEAP trial is an open, randomized, multicenter, Phase I pharmacodynamic study comparing the effects of the AIs L, E and A on safety parameters, such as serum markers of bone formation and resorption, lipid profiles, and adrenal function in healthy postmenopausal women with normal bone mineral density at the spine and hip. Elevated bone biochemical levels indicate high turnover of bone, and correlate with a loss in bone mineral density. It has been suggested that there are differences between the effect of the steroidal AIs (E) and non-steroidal AIs (A and L) on bone turnover, with steroidal AIs having a less negative effect. Methods: Healthy volunteersfrom the UK and Hungarywere randomized to receive A (1 mg/day), L (2.5 mg/day), or E (25 mg/day) orally, once daily for 24 weeks. Changes from baseline in log-transformed bone alkaline phosphatase (ALP), serum C-telopeptide crosslinks (CTX), parathyroid hormone (PTH) and propeptide of type I procollagen (PINP) at 24 weeks on A, were compared with those on L and E by ANCOVA, adjusting for treatment, baseline measurement, BMI, smoking status and baseline estradiol. No adjustments were made for multiple comparisons. Results: A total of 102 healthy volunteers were recruited, with 90 participants evaluable at 24 weeks (29 A, 29 L, 32 E). Participant demographics were similar between the treatment groups in terms of age, years since menopause, and history of hysterectomy and oophorectomy. Bone biochemical measurement changes are presented in the table . With the exception of PTH, where there is a greater decrease in PTH with E than with A (p=0.04), there were no statistically significant differences between the AIs. Conclusions: The steroidal and non-steroidal AIs appear to have similar effects on bone biochemical measurements, and thus bone turnover. All three licensed AIs result in increases in bone turnover.

[Table: see text]

[Table: see text]
Reversal of adverse effects of neoadjuvant chemotherapy on bone turnover in pre- and post-menopausal women with zoledronic acid
Authors: Aft R. , Naughton M. , Trinkuas K. , Watson M. , Weilbaecher K.
Published: March 2020

556

Background: Ovarian failure secondary to adjuvant chemotherapy is known to have an adverse effect on bone mineral density and to increase bone turnover markers. The effects of chemotherapy with growth factor support in the absence of hormonal changes have not been described. The impact of zoledronic acid on these changes was also explored. Methods: We evaluated bone turnover markers in 82 women undergoing neoadjuvant chemotherapy for localized stage II/III breast cancer at initial diagnosis prior to treatment and after 4 cycles of epirubicin (75mg/m2)-docetaxel (75mg/m2) with pegylated G-CSF support with or without zoledronic acid. 47% of patients were post-menopausal and all groups were balanced for other variables. Women were randomized to receive zoledronic acid 4 mg IV every 3 weeks concurrently with chemotherapy (n=41) versus no bisphosphonate treatment (n=41). Bone turnover markers included: urinary N-telopeptide (NTx), serum bone specific alkaline phosphatase (BAP)and osteocalcin (OSTEO). Results: Women, regardless of menopausal status, who received no bisphosphonate had statistically significant increases in NTx, from baseline after 3 months of neoadjuvant chemotherapy using multivariable mixed repeated measures (p=0.0213). Women who received zoledronic acid concurrently with neoadjuvant chemotherapy had statistically significant decreases in NTx (p<0.0001), BAP (p<0.0001) and OSTEO (p=0.0295) from baseline. This is the first demonstration that anthracycline-taxane chemotherapy with growth factor support increased bone turnover markers in both post-menopausal and pre-menopausal women independent of hormone therapy, radiation therapy and surgery. Conclusions: Neoadjuvant chemotherapy with anthracycline- taxane and growth factor support increased bone resorption markers in both post-menopausal and pre-menopausal women. Zoledronic acid given concurrently with each cycle of chemotherapy reversed this increase in bone turnover markers.

No significant financial relationships to disclose.
TPF induction chemotherapy followed by concurrent radiochemotherapy in the first line therapy of advanced carcinomas of the larynx and pharynx (phase IIb trial)
Authors: Knecht R. , Baghi M. , Hambek M. , Zamboglou N. , Tesch H.
Published: March 2020

5562

Backround: Concurrent radiochemotherapy has become a standard procedure for the organ preservation treatment of advanced laryngeal cancer. According to the RTOG 91–11 protocol 2 years larynx preservation and disease free survival rates of 88% and 61% have been described (N Engl J Med 2003;349:2091–8). We perform a phase IIb study answering the question if the addition of triple induction therapy with docetaxel, cisplation and 5FU (TPF) to this regimen is feasible and able to enhance larynx preservation and the disease free survival. Methods: Eligibility criteria have been untreated measurable (RECIST) Stage III/IV carcinomas of the larynx and pharynx in ECOG 0–2 pts. with sufficient organ functions. Planned treatment consisted of 3 cycles induction chemotherapy (every 3 weeks) with docetaxel 75 mg/m2/d1, cisplatin 100 mg/m2/d1 and 5 Fluorouracil 1000 mg/m2/d1–4 (TPF) followed by concurrent radiochemotherapy according to the RTOG 91–11 protocol. Controls have been treated with concurrent radiochemotherapy (RTOG 91–11). One stage design, primary endpoint is recurrence free survival, planned sample size is 250 with 192 events to have a power of 80% to detect a relative risk = 1,432 using a one sided test, alfa = 0.05. Results: 103 patients have been evaluated up to know. Completion of therapy was equivalent in both groups (1/5 drop out rate). Main grade 3/4 toxicities (CTC) during induction chemotherapy were neutropenia (95%) and renal toxicity (25%) and during chemoradiation mucositis (40%) in the chemoradiation group and mucositis (43%), neutropenia (46%) and renal toxicties (24%) in the induction chemotherapy group The toxicities were reversible. After induction chemotherapy the ORR was 84% with a CR of 55%. After the completion of therapy the ORR in the induction chemotherapy group (IC) was 97% versus 93% in the chemoradiation group (RC). After a median follow up of two years the larynx preservation rates and the disease free survival rates are as follows:91% (IC) vs. 87% (CR), n.s., and 85% (IC) vs. 66% (RC), p = 0.017. Conclusion: Addition of TPF induction therapy to the RTOG 91–11 concurrent radiochemotherapy protocol may enhance the disease free survival.

No significant financial relationships to disclose.
Long term follow up data of a phase II study of concurrent radiotherapy (RT) and gemcitabine (Gem) for patients with stage III or IV squamous cell carcinoma of the head and neck (SCCHN)
Authors: Specenier P. M. , Van Den Weyngaert D. , Van Laer C. , Van Den Brande J. , Huizing M. , Altintas S. , Vermorken J.
Published: March 2020

5574

Background: RT with concurrent chemotherapy is superior to RT alone as treatment for locally advanced SCCHN. Gem is a potent radiosensitizer in vitro and in vivo and in addition has a good activity in SCCHN. Exploitation of these properties was the rationale for a single institution phase II study which evaluates the efficacy and toxicities of standard RT + weekly low dose Gem. Methods: Eligible were patients with primary inoperable or locally advanced stage III and IV SCCHN. Treatment: Planned RT was 70 Gy over 7 weeks with weekly Gem 100 mg/m2 within 2 hours prior to RT (Eisbrüch et al., ASCO, 1997, 1998). Presented endpoints are response rate (according to WHO), acute and late toxicity (according to NCICTC), disease free survival (DFS), local relapse free survival (LRFS) and overall survival (OS). Results: 26 patients (21 male, 5 female; performance status 0–2; no prior treatment) entered the study between November 1998 and September 2003. Median age was 56 years (range 48–78). Tumor sites were oropharynx (6), hypopharynx (17), glottis (1), paranasal sinus (1), unknown (1). Clinical stage was III (2) or IV (24). 7 Patients had T4N2 disease and 2 had T4N3 disease. Patients received a median of 7 Gem cycles (range 2–8) and a median of 70 Gy (66–84.75). 7 patients underwent radical neck dissection. Grade 3–4 acute toxicities included mucositis (22/26), dermatitis (18/26), pharyngitis and/or oesophagitis (21/26), pain (7/25), xerostomia (1/24), neutropenia (1/26) and anemia (1/26). 21/26 patients needed tube feeding and 21/26 needed to be hospitalized. After recovery from acute toxicity 6/23 could feed normally, 5/23 needed soft food, 5/23 were able to swallow liquid food and 2/23 required permanent tube feeding. Response was evaluable in 22 patients (11 CR, 11 PR). Intial relapse was at distant sites in 9/26 and local in 8/26. Median follow up of the patients still alive is 46 months. Median OS is 576 days, median DFS is 401 days, median LRFS is not reached. 7/26 remain free of disease more than 3 years after end of treatment. Conclusions: RT + Gem (100 mg/m2/week) is feasible but toxic. The combination is highly active in SCCHN and provides a good long term local control.

[Table: see text]
Concurrent split course hyperfractionated radiotherapy (Hfx RT) with biweekly cisplatin (DDP) and paclitaxel (P) in patients with recurrent, previously irradiated squamous cell carcinoma of the head and neck (SCCHN): The MUSC experience
Authors: Sawhney R. , Dragun A. , Stuart R. K. , Chaudhary U. B. , Day T. , Gillespie M. B. , Sharma A.
Published: March 2020

5578

Background: Locally recurrent disease (RD) contributes to the majority of SCCHN-related deaths. In addition, second primary tumors (SPT) develop in approximately 30% of patients (pts) who were cured of their primary malignancy. For pts with disease (RD or SPT) in a previously irradiated region, therapeutic options are limited. Approaches utilizing reirradiation with concurrent chemotherapy (CT) have been investigated, with promising initial results. We retrospectively report the clinical outcome & toxicity of such a regimen. Methods: A cohort of pts with locally recurrent or second primary SCCHN within previous radiation portals were treated with concurrent chemoradiotherapy (CRT). Pts received HFx RT (1.5 Gy/Fx BID × 5 every 2 wks × 4), in combination with DDP 15 mg/m2 IV QD × 5 and P 20 mg/m2 IV QD × 5 q 2 wks × 4. Filgrastim was given on days 6–13 of each 2 wk cycle. Results: Nineteen pts were treated (median age 61; 84% with RD at median of 22 mos, 16% SPT; primary site: oropharynx-32%, larynx-32%, oral cavity 21%). Two pts had treatment discontinued early (due to hemoptysis & declining performance status, respectively). Seventeen pts were evaluable at a median f/u of 13 mos. Acute skin & mucous membrane toxicity (Grade ≥ 2) was seen in 11% and 5% of pt’s, respectively, and 32% of pts developed skin fibrosis as a late radiation toxicity. Most pts (82%) received all 4 scheduled cycles of CT. Grade ≥ 3 hematologic toxicity occurred in 29% of pts (anemia 24%, neutropenia 24%, & thrombocytopenia 12%). Infection was the primary non-hematologic toxicity, with Grade ≥ 3 infection in 29% (4 pneumonia, 1 vascular catheter). There was 1 treatment-related death (hypotension with CVA). Of the 16 pts who completed treatment, 4 had initial surgery, and thus had no measurable disease upon commencing CRT. Objective responses to CRT were noted in all of the remaining 12 pts and 50% achieved a CR. One-year OS rate was 65%, with median survival not yet reached. Conclusions: RD and SPT pts who are not surgical candidates have limited treatment options. Aggressive reirradiation with biweekly CT produces excellent response rates, with acceptable local and systemic toxicities.

No significant financial relationships to disclose.
Understanding resistance to hormonal therapy in estrogen avid breast cancer
Authors: Linden H. M. , Stekhova S. , Link J. M. , Livingston R. B. , Gralow J. R. , Ellis G. K. , Peterson L. M. , Schubert E. K. , Krohn K. A. , Mankoff D. A.
Published: March 2020

566

Background:
The estrogen receptor (ER) is an essential target for endocrine therapy in breast cancer. We, and others, have tested an in vivo assay of ER function, [F-18]-16α-fluoroestradiol (FES) PET, which allows assessment of all sites of tumor spread and predicts response to hormonal therapy. However, not all patients with tumors bearing functional ER respond to therapy, suggesting the presence of mechanisms of resistance other than ER loss.
Methods:
65 postmenopausal female patients with known ER+ metastatic (mostly bone and soft tissue dominant) breast cancer treated with aromatase inhibitors underwent PET FDG and FES imaging on an institutional imaging protocol (majority in second-line therapy). Hormone levels were assayed at the time of imaging, and biopsy specimens from either the primary tumor or metastasis were analyzed for expression of ER, PR, AR, PSA, HER2neu, and TopoIIα.
Results:
49 (75%) patients had at least modest levels of retained ER expression, indicated by an average FES SUV > 1.5 at the tumor sites. We found serum estradiol, or estrone, levels >30pg/ml in 30% of patients. We found the majority of patients had PR, or AR expression, but few had EGFR or TopoIIα expression. FES SUV > 1.5 predicted response to therapy (p=.0006); no patient with an FES SUV < 1.5 had an objective response. Only 18/49 patients with SUV >1.5 responded to AI therapy. In the subset with FES SUV > 1.5, factors predicting lack of response to AI included PR negativity (p=.038) and/or detectable serum estradiol levels (p=.05).
Conclusions:
Quantitative PET FES predicts response to hormonal therapy. Estrogen levels may not be completely suppressed in patients on long-term AI therapy. Estradiol levels > 30pg/ml and lack of PR expression predict resistance to endocrine therapy in patients with tumors bearing functional ER expression. Efforts to monitor and reduce estradiol levels may offer therapeutic benefit to patients.

No significant financial relationships to disclose.
Comparison of neoadjuvant 6 vs 8 cycles of docetaxel/doxorubicin/cyclophosphamide (TAC) in patients early responding to TACx2-the GEPARTRIO Study
Authors: Von Minckwitz G. , Blohmer J. , Vogel P. , Hanusch C. , Eidtmann H. , Hilfrich J. , Gerber B. , Huober J. , Costa S. , Kaufmann M.
Published: March 2020

576

Background: Primary breast cancer (BC) patients (P) with early response to neoadjuvant TACx2 (75mg/m, 50 mg/m, 500 mg/m, day 1, q21, supported with (pegylated) G-CSF and epoetin) experience a high pathologic complete remission (pCR) rate after further TACx4 (von Minckwitz et al, Ann Oncol 2005) compared to patients without early response (SABCS 2005, Abst 38). We compared prolongation to 8 cycles of TAC with conventional 6 cycles TAC in the chemosensitive subgroup. Methods: P with operable (T 2 cm by palpation) or locally advanced (T4 or N3, M0) BC were treated with TACx2. If tumor reduction was exceeding 50% according to breast ultrasound, P were randomized to receive either 4 or 6 additional cycles. Endpoints were pCR-rate (no invasive and no non-invasive residuals) (primary), sonographic response before surgery, breast conservation rate, safety and compliance (secondary). To detect an increase in pCR-rate from 20 to 26%, 606 evaluable patients were requested for each arm (α=0.05, β=0.2, one-sided). Results: 2106 P were recruited into the multi-centre, prospective, open-label, randomized GEPARTRIO-trial within 36 months. 1400 P with an early response to TACx2 were randomized with the last patient having surgery in Dec 05. Median clinical tumor size was 4.0 (1.0 - 30.0) cm at study entry. A planned safety and blinded efficacy interim analysis was performed on the first 600 patients (306 TACx6, 294 TACx8). Main toxicities (grade I-IV %TACx6 vs %TACx8) were: anemia (91 vs 93), thrombopenia (39 vs 49), neutropenia (65 vs 75), febrile neutropenia (10 vs 16), infection (29 vs 30), vomiting (42 vs 44), diarrhea (59 vs 52), stomatitis (66 vs 67), conjunctivitis (51 vs 57), allergic reactions (20 vs 14), edema (40 vs 47), asthenia (90 vs 93), hand-foot-syndrome (25 vs 28), nail (43 vs 50), dyspnea (33 vs 37), sensory neuropathy (51 vs 61). Treatment was discontinued early in 165 P (31.0%), 53 (19.8%) P during TACx6 and 112 (42.3%) P during TACx8. Overall pCR was reported in 102 (17.0%) of these patients. Conclusions: TACx8 is associated with moderate increase in toxicity and treatment discontinuations compared to TACx6. Final results on the primary and secondary endpoints will be presented.

[Table: see text]
BAY 43–9006 as single oral agent in patients with metastatic breast cancer previously exposed to anthracycline and/or taxane
Authors: Moreno-Aspitia A. , Hillman D. W. , Wiesenfeld M. , Hobday T. J. , Rowland K. M. , Northfelt D. W. , Tenner K. S. , Palmieri F. M. , Perez E. A.
Published: March 2020

577

Background:
BAY 43–9006 targets the ras/raf signaling pathway and inhibits VEGFR-2, VEGFR-3 and or PDGFR-β growth factors. A study was conducted to assess anti-tumor activity and the toxicity profile in patients (pts) with metastatic breast cancer (MBC).
Methods:
A two-stage phase II study was conducted with pts with MBC who had measurable disease and were candidates for 1
st
or 2
nd
line chemotherapy and had previously received an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic setting. Pts started with a dose of 400 mg twice daily on days 1–28 of each 4 week cycle. Based on interval adverse events (AEs), a dose reduction was considered as 400 mg given one time daily. Primary endpoint was tumor response defined as a complete or partial response (PR) according to RESIST. The study required 40 pts, but was to be terminated if 0 or 1 responses occurred among 1
st
20 eligible pts.
Results:
23 pts enrolled with a median age of 54 (range 37–70) but 3 were declared ineligible. All 23 pts were included in all analyses except efficacy analysis as stated per protocol. Fifteen (65%) had visceral metastasis; 22 (96%) had prior anthracycline treatment (tx); 16 (70%) had prior taxane tx.; 10 (44%) had received prior chemotherapy for metastatic disease and 14 (61%) had a prior relapse free interval of 12 months (mos) or more. Pts received tx for a median of 2 cycles (range 1–8) with a median follow-up of 7.2 mos. Dose reductions were due to dermatitis/skin rash (3), hand/foot skin reaction (2), hypertension (1) and cramping hands/feet (1). No grade 4 AEs occurred and grade 3 AEs included acne (2), hand/foot skin reaction (1), neutropenia (1), cough (1), wound infection (1), and prolonged PTT (1). Among the 20 pts eligible for efficacy analysis one pt (5%; 95% CI 0.5–20.5%) achieved a PR with duration of 3.6 mos and one pt achieved stable disease for at least 6 mos. The 6-month overall survival rate was 81% and the progression-free survival rates were 53% at 2 mos, 24% at 4 mos and 6% at 6 mos. Median time to progression was 2 mos. Based on the lack of sufficient response, we did not proceed with the 2nd stage of this study.
Conclusion:
Treatment with oral BAY 43–9006, while well tolerated, does not have sufficient activity to warrant further testing as a single agent in this disease setting.

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Changes in circulating endothelial cells (CEL) in patients receiving trastuzumab for metastatic breast cancer predict response to treatment
Authors: Spadaro P. , Ingemi M. , Dottore G. , Toscano G. , Maisano R.
Published: March 2020

579

Background: Amplification or overexpression of HER-2/neu has been identified in 10–20% of invasive breast cancers and is associated with shorter overall survival times; furthermore HER-2/neu is a predictive factor with regard to monoclonal antibody therapy with Trastuzumab. The observed association between the overexpression of HER-2/neu and higher VEGF expression indicates that HER-2/neu is involved, at least partly, in the regulation of angiogenesis in human breast cancer. Recently circulating endothelial cells (CECs) have been proposed as a marker of tumor progression and/or a response to antiangiogenic therapy; thus, we have performed a phase II study to explore the correlation between CECs and treatment with Trastuzumab in metastatic breast cancer Methods: 22 women aged ≥ 18 years with histologically proven Her-2-positive, ECOG performance status 0 to 2 who were not eligible for, or who wished to delay receiving chemotherapy received a standard loading dose of Trastuzumab 4 mg/Kg followed by 2 mg/Kg weekly. The weekly maintenance dose was continued until disease progression. A panel of monoclonal antibodies including anti CD45 to exclude hematopoietic cells, anti CD31, CD34, CD36, CD105, CD106, CD133, and KDR and appropriate analysis gates were used to enumerate resting and activated circulating endothelial cells Results: The overall response rate (RC + RP) to treatment was 25% (2 RC + 3RP). In healthy controls (N° 20) mean values of resting and activated CECs were 7.6/μL (4.6 - 11.2/μL) and 1.3/μL (0.1 - 2.4 /μL) respectively. Before treatment with Trastuzuamb the mean resting and activated CECs were 41.1/μL (16.4 - 60.5/μL) and 6.9/μL (5.1 - 8.7/μL). At a first assessment (6 wks) a significant decrease in CECs (p<0.001)was found in patients responding to treatment but not in the patients who did not achieve a remission Conclusions: Our finding has shown that resting and activated CECs are increased in metastatic breast cancer patients and decline during treatment in responding patients, furthermore, these data underline the crucial role of angiogenesis in this setting and support the rationale for a combination of Bevacizumab with Trastuzumab.

No significant financial relationships to disclose.
Male breast cancer (MBC) in the VA population: A gender issue?
Authors: Nahleh Z. , Srikantiah R. , Komrokji R. , Safa M. , Pancoast J. , Muhleman A. , Jazieh A.
Published: March 2020

587

Background: The incidence of MBC continues to rise. Few studies have addressed the differences between MBC and female breast cancer (FBC). Treatment for MBC has ben extrapolated from FBC regimens. The VA cancer registry (VACCR) provides a unique source to study MBC. This retrospective analysis aims at comparing the characteristics and outcome of MBC and FBC in the VA population. Methods: We reviewed the VACCR database between 1995 and 2005, for 120 VA medical centers. Primary breast cancer site codes were identified (500–508). Data was entered and analyzed using bio-statistical software SPSS. Results: A total of 3025 patients :612 MBC and 2413 FBC were compared. Mean age at diagnosis was 67 for MBC and 57 for FBC (p <0.005). More MBC patients were black. MBC patients presented with a significantly higher stage of disease, more node positive(N+) and larger tumor size. In MBC, ductal histology was more common while lobular and ductal carcinoma in situ were less common than in FBC. ER + and PR + tumors were significantly more common in MBC (60% vs 52% and 53% vs 47%, P< 0.005). MBC patients received less chemotherapy while no statistical difference in hormonal treatment was observed. The median overall survival (OS) was lower for MBC (7 years vs 9.8 years, p<0.005). OS was not significantly different for stage III and IV while OS was inferior for MBC in stage I (7 yr vs not reached, p 0.005) and stage II (6 vs 8.6yr, p 0.001). In N- tumors, OS was inferior in MBC (6.1 vs 14.6 yr, p<0.005) but not statistically different for N+ tumors . In ER + and PR + tumors, OS was inferior in MBC (7yr vs 8yr and 7.3 yr vs 9.8 yr p<0.005); however, no statistical significance was observed in ER - or PR - tumors. Using Cox regression analysis age, sex, clinical stage, nodal status were statistically independent prognostic factors while race, histology and grade were not. Conclusion: This study suggests differences in the biology, pathology, presentation, and survival between male and female VA breast cancer patients. Survival of MBC patients appears inferior in early stage disease and N- tumors suggesting gender differences in the tumor pathogenesis and biology. In hormone receptor + MBC, survival was also inferior despite similar hormonal treatment practices. This observational study calls for different approach and treatment strategies in MBC.

No significant financial relationships to disclose.
Breast cancer treatment patterns of Asian-American women in an equal access system
Authors: Kang S. K. , Ely B. W. , Riffenburgh R. H. , Chung T. S. , Chan A. D. , Hu J. S.
Published: March 2020

589

Background: Treatment patterns of breast cancer in Asian-American women have not been well studied. Existing studies suggest higher mastectomy rates compared to Whites, but have been unable to control for differences in access to healthcare. The objective was to describe primary and adjuvant treatment patterns of Asian women in an equal-access healthcare system. Methods: Data were extracted from the tumor registry to include women diagnosed with T1-T2, M0 breast cancer between 1989 and 2004 and treated at the Naval Medical Center San Diego, an equal-access system. Self-reported data was used to classify race. Military rank was used as a proxy for socioeconomic status and education level. Characteristics and treatment patterns of Asian and White women were compared by the two-sided Fisher’s exact test and multiple logistic regression with consideration of covariates. Results: 574 non-Hispanic White and 226 Asian-American women resulted from the query. Asian women received mastectomy more often than Whites. From 1989 to 2004, mastectomy rates declined for both groups at an equal rate until 1997. On secondary analysis based on the initial results, differences in mastectomy rates existed only until 1997, which was coincident with the opening of a multidisciplinary Breast Health Center. Asians were much less likely to receive breast reconstruction. There was no difference in rates of adjuvant radiation or chemotherapy, but a suggestion of higher hormone therapy rates in Asians. Conclusions: Even in the setting of an equal-access healthcare system, Asian-American women were more likely to receive mastectomy than Whites, suggesting that barriers to healthcare access do not explain these treatment disparities. This difference disappeared in recent years. The contrasting reconstruction rates suggest a difference in cultural attitudes regarding the significance of the breast in the setting of cancer treatment. The multidisciplinary Breast Health Center may have ameliorated factors leading to higher mastectomy rates in Asians.

[Table: see text]

No significant financial relationships to disclose.
Age frequency distribution of joint ER/PR phenotypes in primary breast cancer patients: An analysis of 3,620 cases at a single Japanese institute
Authors: Saji S. , Ishizuka N. , Horiguchi K. , Suzuki E. , Bando H. , Aruga T. , Takahashi I. , Tominaga T. , Toi M.
Published: March 2020

597

Background:
Hormone receptor (HR) expression may reflect the different subtypes of breast cancer. Recent clinical trials have reported that joint Estrogen receptor (ER)/Progesterone receptor (PR) phenotypes in breast cancer have specific spectrum for treatment response. To analyze the epidemiologic character of ER/PR subtypes in Japanese patients, a retrospective data survey was conducted for 3,620 breast cancer patients treated at a single institute during 1975–2005.
Methods:
Patients records were obtained from cancer registration of the Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital and analyzed with SAS software. Among 3,620 operated patients, data of ER/PR subtypes were available in 2,707 cases. HRs were evaluated by ligand binding assay (LBA) or enzyme immuno assay (EIA) from 1975 to 2000 (n=1721), and by immunohistochemistry (IHC) after that (n=986).
Results:
Both mean and median of patient’s age increased through the operated year (p<0.0001). Therefore, all analysis related to distribution of age were adjusted by the operated year. As reported before, ER+ population showed liner trend with age by LBA/EIA (p<0.0001), while this was not observed by IHC. ER-/PR+ population was 10.6% by LBA/EIA, whereas it decreased to 2.1% by IHC. These are due to the increase of ER+ population with IHC analysis, since marginal distribution between two methods in the patients tested by both assays was significantly different for ER, but not for PR (n=181, p=0.0038 and n=175, p=0.1944). Irrespective of assay methods, peak age frequency of ER+/PR+ was between 46 and 50 years of age, whereas that of ER+/PR- was 56–60. For ER/PR phenotypes there was a significant difference of odds ratio across the age (<55 vs. ≥55, p=0.04 for IHC, p=0.0002 for LBA/EIA).
Conclusion:
Changes of standard assay from LBA/EIA to IHC affected the population of ER+ and lead the decrease of ER-/PR+ subtype. Japanese women’s peak age frequency of ER+/PR+ was in the premenopausal period compared to that of non-Hispanic white women in the postmenopausal age (Anderson WF, JCO 2001). Difference of most frequent age of each subtype among the races may be taken into account for the development of chemoprevention strategy with anti-estrogens.

No significant financial relationships to disclose.
A randomized controlled trial (RCT) of long-term follow-up for early stage breast cancer comparing family physician to specialist care: A report of secondary outcomes
Authors: Grunfeld E. , Julian J. , Levine M. , Pritchard K. , Coyle D. , Dent S. , Verma S. , Mirsky D. , Sawka C. , Ginsburg D. , Wood M.
Published: March 2020

6003

Background: Breast cancer patients usually receive follow-up in specialist cancer clinics. We have reported that family physician follow-up of breast cancer patients is a safe and acceptable alternative to specialist follow-up as measured by the primary clinical outcome of the rate of serious clinical events (Grunfeld et al, JCO 2006;24(6)). We report here the secondary outcomes of this trial: quality of life domains, patient satisfaction and patients’ costs. Methods: Women with early stage breast cancer who had completed adjuvant therapy (patients may have continued on adjuvant hormonal therapy), who were disease free and between 9 and 15 months after diagnosis, were allocated to receive follow-up in a cancer clinic according to usual practice (CC arm) or follow-up from their own family physician (FP arm). For patients without recurrence, quality of life (QL) measured by the SF36, patient satisfaction, and patients’ costs were measured every 6 months. For patients with recurrence QL measured by the EORTC QLQ C-30 was measured at the time of recurrence. Results: 483 patients were allocated to the FP arm and 485 to the CC arm. Median follow-up was 3.5 years. There were no significant differences between groups on change scores for SF36 subscales to 24 months, or EORTC functional subscale scores at the time of recurrence. Patients’ costs of follow-up (travel costs, out-of-pocket expenses, and lost earnings) were significantly less to 24 months (p < 0.02) in the FP arm. Although costs were less between 36 and 48 months, these were not significant. Conclusions: Family physician follow-up of breast cancer patients does not have a negative impact on clinical or QL outcomes and is less costly for patients.

No significant financial relationships to disclose.
Impact of a mass media campaign (MMC) on awareness of and willingness to participate in cancer clinical trials (CCT): Results from 2,269 survey respondents
Authors: Umutyan A. , Lara P. N. , Chiechi C. , Turrell C. , Chen M. S. , Paterniti D. A. , Wun T. , Davis S. , Gonzalez J. , Beckett L. A.
Published: March 2020

6012

Background: Annually, only 3% of patients (pt) participate in CCT. Accrual barriers include lack of CCT awareness and uncertain third party coverage. In 1/02, a California law (SB37) required all third party payers to reimburse pt care costs related to CCT. We sought to increase awareness of CCT/SB37 through a MMC, and assessed willingness to participate. Methods: Following a pre-MMC survey of 1,188 cancer pt and/or their caregivers’ awareness and willingness levels (JCO 2005; 23:9282–89), a TV/radio/print/internet MMC was conducted in a 9-county catchment area for UC Davis Cancer Center from 4/05–6/05. The MMC emphasized CCT/SB37 availability and used an iconic “Big C” logo. The survey was repeated post-MMC in two pt/caregiver cohorts: from the UC Davis Cancer Center catchment area (C1), and a control group from the UC San Diego area (C2) who did not see the MMC. Changes in CCT/SB37 awareness and willingness to participate were probed pre- vs. post-MMC and C1 vs. C2 by Pearson χ2 & logistic regression. Results: Of 2,269 respondents, 1,081 were post-MMC: 957 from C1 and 124 from C2. Post-MMC respondents differed from pre-MMC by respondent type (pt > caregivers), age (older), race (more blacks), and income (more $75k+/yr). Pre- vs. post-MMC, C1 respondents had greater awareness of CCT (59% to 65%, p < 0.01) and SB37 (17% vs. 32%, p < 0.01); no significant change was seen in C2. Adjustment for demographic variables in C1 resulted in p > 0.05 for CCT/SB37 awareness. Willingness to participate in CCT did not change pre- vs. post-MMC in C1 or C2. Awareness level predicted willingness (OR = 2.3, p < 0.01), but this was not true for the lowest income/education groups. Blacks/Asians/lowest income (< $25K/yr) groups were least willing to participate (p < 0.01/0.04/0.02). Conclusions: Although CCT/SB37 awareness increased in C1 following the MMC, it is unclear whether this was wholly attributable to the MMC due to varying demographic variables. Awareness of CCT/SB37 did not universally translate into willingness to participate in all subgroups. Enhancing pt willingness (to increase CCT accrual) will require targeting other variables, such as physician or resource barriers, rather than just CCT/SB37 awareness. (R21 CA-03501).

No significant financial relationships to disclose.
Diagnostic assessment of suspected cancer: Prospective cohort study of diagnostic delay intervals across three disease sites
Authors: Watters J. , Grunfeld E. , Jaffey J. , O’Rourke K. , Maziak D. , Patel D. , Morash C. , Evans W. K.
Published: March 2020

6029

Background: Diagnostic assessment of patients with suspected cancer can involve multiple points of delay. Methods: We conducted a cohort study of prospective eligible patients referred to a regional hospital in Ottawa, Ontario, Canada over a 12 month period (2004 to 2005) for diagnostic assessment of suspected colorectal (C), lung (L) or prostate (P) cancer. The study addressed three different disease sites, each with a different pre-existing model of care delivery, so that variability could be described. Measurement of diagnostic delay intervals included days to diagnosis (from referral to diagnosis communicated to the patient) and, for patients with cancer, to surgery and to oncology consultation. Differences between disease sites for diagnostic delay intervals, quality of life, and patient satisfaction were analyzed. Results: The proportion of patients who were diagnosed with cancer was: 6.8% (9/132) for C; 80.2% (81/101) for L; and 35% (41/116) for P. The mean [SD] days to diagnosis was significantly less for L (45 [32]) than for either C (81 [68]) for P (82 [43]), (p=.0001). It was also significantly less for patents diagnosed with cancer (57.8)[41.4]) than for those without cancer (79.3)[58.9]) (difference -21.5; 95% CI -33 to -9; p=.0003); a finding which held when C was analyzed separately (33.8 [48.9] vs 84.8 [67.7]; p=.04). L patients had worse physical and mental functioning as measured by the SF36 Physical and Mental Component Scores. Patient satisfaction did not differ across disease site or for patients with and without cancer. Conclusions: Most studies of diagnostic delay intervals use administrative data. This study is unique in prospectively measuring intervals that cannot be captured from administrative data and thus provides important benchmark measures. L patients were most likely to have cancer. Although C patients were unlikely to have cancer, the diagnostic interval was substantially shorter in those with cancer than in those without, suggesting that clinicians have an effective process for triaging patients referred for diagnostic assessment.

No significant financial relationships to disclose.