Background

BM in HER2-positive BC patients are increasing, without agreement on the appropriate treatment of this subgroup. The disrupted blood-brain barrier in the setting of BM may allow the penetrance of T-DM1, with little evidence of its efficacy in this situation.

Methods

HER2-positive BC patients treated with T-DM1 monotherapy at Ramon y Cajal Hospital (Madrid) from 2012 to 2017 were eligible. We differentiated patients without BM, stable BM (those with BM who had received local treatment for them and they were not in progression) and progressive BM (those who were in brain progression to a local treatment) at the beginning of T-DM1. We collected hormone receptors (HR) status, neoadjuvant treatment, number of previous treatments for metastatic BC, patients who received taxanes, pertuzumab or both, sites of metastatic disease, duration of T-DM1 and sites of progression. We analysed progression free survival (PFS) in total population and in both subgroups (patients with or without BM).

Results

We identified 29 patients, 69% had positive HR, 45% had received neoadjuvant treatment and 55% had received 2 or more prior lines of treatment. Of total, 97% received taxanes and 38% received pertuzumab. Most patients had visceral disease. Patients received a median of 5 cycles of T-DM1, median duration of T-DM1 was 13 weeks and 4 remain on treatment at time of analysis. Before starting T-DM1, 28% had known BM (75% stable, the rest in progression). Only 10% of patients had cerebral progression during T-DM1. 19 patients had systemic progression during T-DM1, 2 of them with brain progression at same time, and 9 patients presented brain progression after finishing T-DM1. Median PFS was 21 months (m) in total population (confidence interval [CI] 95%: 12,58-28,94), 5 m in patients with BM (CI 95%: 3,88-6,50) and 24 m in those patients without BM when T-DM1 was started (CI 95%: 12,58-28,94). T-DM1 showed benefit in terms of PFS in patients without BM at the beginning of treatment in comparison with those with baseline BM (HR 0,297, p = 0,014).

Conclusions

T-DM1 seems to be an effective therapeutic option in unselected HER2-positive BC patients with BM, but these findings require a prospective validation.

Legal entity responsible for the study

Elena López Miranda, Roberto Martín Huertas.

Funding

Roche Pharma.

Disclosure

All authors have declared no conflicts of interest.

Background

Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost. The optimal duration of filgrastim as primary FN prophylaxis in early stage breast cancer (EBC) patients is unknown. We compared the cost-effectiveness of 5, 7 or 10 days of filgrastim offered for primary FN prophylaxis.

Methods

We conducted a cost-utility analysis from the perspective of Canada’s health care system using a decision tree to evaluate the costs and quality-adjusted life years (QALYs) based on the results of the REaCT G study. In this study EBC patients who were to receive adjuvant chemotherapy were randomized to 5 versus 7 or 10 days of filgrastim as primary FN prophylaxis. Using EQ-5D-5L measures from patients at baseline, after one cycle and at the completion of chemotherapy, along with the cost of complications of febrile neutropenia and treatment-related hospitalization from the provincial database, we determined incremental cost-effectiveness ratio (ICER) for the 7 or 10 days of filgrastim compared to 5 days. Both deterministic and probabilistic sensitivity analyses were carried out.

Results

From 464 patients on the REaCT G trial showed that 5 & 7 days compared to 10 days filgrastim were associated with lower costs and a slight decrease in QALYs. Compared to 5 days of filgrastim, 10 days was associated with an increase cost $3,763 and 0.019 QALYs with ICER of $198,052, and 7 days of filgrastim led to a rise in cost by $2,461 and QALYs by 0.004 with ICER of $615,250. The probabilistic sensitivity analysis showed that cost-effectiveness results were uncertain. At commonly willingness to pay threshold of $50,000/QALY, probabilities that 5, 7 and 10 days filgrastim are cost-effective were 48%, 35%, and 18%, respectively.

Conclusions

We conclude that shorter schedules of filgrastim provide cost savings with a slight decrease in QALY. The schedule of filgrastim prophylaxis that would be considered cost-effective depends on the willingness of the payer.

Legal entity responsible for the study

Mark Clemons.

Funding

REaCT Program and Cancer Care Ontario.

Disclosure

All authors have declared no conflicts of interest.

Background

BRCA testing rates, treatment patterns and outcomes were compared based on BRCA mutation status in HER2- adult women with ABC.

Methods

Oncologists extracted data from patient charts in adult women with HER2- ABC across the US and France, Germany, Italy, Spain and the United Kingdom (EU5) via the Adelphi Advanced Breast Cancer Disease Specific Program. Data drawn from 2015 and 2017 were merged across common variables. Patients were categorized into three mutually exclusive cohorts; BRCA mutations (BRCAm), wild type (BRCAwt), and unknown status (BRCAunk). Treatments received and 1^st line duration of therapy was compared between BRCAm and BRCAwt using Fisher exact, Mann-Whitney tests, and t-tests.

Results

The study included 6,161 adult women with HER2- ABC (4,611 hormone receptor positive [HR+/HER2-], 1,415 triple negative breast cancer [TNBC], 135 unknown hormone status). Overall, 28% of patients received ≥1 BRCA test at any point in their lifetime (23% HR+/HER2-, 41% TNBC). 235/6,161 (4%) patients were identified as BRCAm, 1,025/6,161 (17%) as BRCAwt, and 4,901/6,161 (80%) as BRCAunk. Within the HR+/HER2- cohort, patients with BRCAm were more likely to receive 1^st line chemotherapy compared to BRCAwt (65% vs 49%; P = 0.005) and less likely to receive endocrine +/- targeted therapies (33% vs 49%; P = 0.003). TNBC treatments consisted primarily of chemotherapy and were similar between BRCAm vs. BRCAwt, (89% vs. 91%; P = 0.545). Mean duration among patients who completed 1^st line treatment was numerically shorter for patients with BRCAm [Table].

Table: 161P

1^st line duration of therapy (mean months [SD]) based on BRCA status

Conclusions

In this study of adult women with HER2- ABC, low BRCA testing rates were observed. Patients with BRCAm were significantly more likely to utilize chemotherapy relative to BRCAwt. Mean duration of 1^st line therapy was numerically lower among patients with BRCAm. With the advent of new treatment options, additional studies are warranted to validate these findings.

Legal entity responsible for the study

Pfizer.

Funding

Pfizer.

Disclosure

A. Niyazov: Employee, stockholder: Pfizer; R.G.W. Quek: Employee, ownership interest: Pfizer. All other authors have declared no conflicts of interest.

Background

Breast to bone metastasis is a common event during breast cancer progression. The resultant lesions are painful and currently, despite medical advances, are incurable. Therefore, identifying the underpinning molecular mechanisms in the bone microenvironment is vital for the development of new therapies. Gene expression analysis and validation in human and murine specimens of bone metastases revealed matrix metalloproteinases, such as MMP-2, are highly expressed in the bone metastatic microenvironment. These data support the rationale for the development of a highly specific MMP-2 inhibitor for the eradication of active bone metastatic breast cancer.

Methods

Given that previous broad-spectrum MMP inhibitor (MMPI) trials were unsuccessful due to dose limiting systemic side effects, we utilized a novel chemical approach to synthesize bone seeking MMP inhibitors (BMMPIs) on a bisphosphonic backbone, with specificity for MMP-2 in the nanomolar range (IC50=140 nM). Based on our previous data about BMMPI’s ability to significantly reduce breast cancer growth in the bone microenvironment, we decided to investigate the role of BMMPI such as ML115 in preventing dissemination of cancer cells into the skeleton. Balb-c female mice (n = 10/group), pretreated for 7 days with vehicle, standard of care bisphosphonate (Zoledronate= 1 mg/kg) and BMMPIs (ML115= 1 mg/kg), were randomized and intra-cardiac injected with luciferase expressing 4T1 (2x10⁵) breast cancer cell line. Tumor growth was assessed via luminescence quantitation overtime.

Results

Our preliminary total body bioluminescent data suggest that pretreatment with ML115 can significantly reduce the amount of breast cancer cells homing into the bone, compared to vehicle and standard bisphosphonate. Cancer induced bone disease was measured ex vivo by μCT, Xray and histomorphometry. Ex vivo analysis also illustrated the significant beneficial effects of the BMMPIs in reducing the size of osteolytic lesions. We are currently measuring MMP activity in vivo and ex vivo via specific activatable MMP probes, in order to confirm BMMPI mechanism of action.

Conclusions

We predict that BMMPIs could be used as preventive treatment to impair breast cancer to bone metastasis in clinic.

Legal entity responsible for the study

H Lee Moffitt Cancer Center.

Funding

Susan G Komen Breast Cancer Foundation and American Airlines.

Disclosure

All authors have declared no conflicts of interest.

Background

The negative pressure therapy (NPWT) is usually used to treat difficult and chronic wounds. Among NPWT devices, some of them, like PICO, have a proven utility as a prophylaxis against surgical wound complications in high risk patients. PICO is a fixed intensity instrument, working with a continuous -80mmHg pressure over the wound.

Methods

In the MARIPI study 100 high risk patients have been enrolled, 50 of them received a PICO plaster directly in the surgical room. We have then evaluated the difference in incidence of surgical wound complications between the case and control groups.Patients have been considered eligible to our study in the period 01.01.2016 to 01.01.2017 due to one or more of these following risk factors: diabetes, heavy smoke (more than 10 cigarettes per day), previous radiotherapy in the thoracic fields, skin diseases, vascular or cardiac alterations.

Results

After a deep results analysis, significant difference in the wound infection rate comes out: 1(4.3% ) in the PICO group vs 3 (13,0%) in control group. The same consideration can be made concerning the wound dehiscences: 2 (8.7%) in the PICO group, 6 in the control one (26,1%). (p = 0.093) The whole number of patients’ clinical checks was 113 in the PICO group and 150 in the control one (p < 0.001) Medications with negative pressure reduce the wound infection rate down to about 50 and the dehiscence rate of about 66%, and this can lead to a costs reduction even considering the cost of 200$ (about 130 €) for any PICO medication.

Conclusions

In our opinion, similarly to what may be found in the literature concerning other kinds of surgery, the use of PICO for risk reduction is justified in high risk patients. Further and broader randomized studies are in any case needed to better clarify the role of the therapies with negative pressure in breast cancer patients.

Legal entity responsible for the study

AUSL Romagna.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

As a rare disease, knowledge about management of male breast cancer (male BC) is scarce but increasing in the last years. Still, according to RARECAREnet study, 5-year relative survival in Bulgarian male BC patients is 18% less than European mean. We look for potential reasons for this low survival rate; we also identify trends or gaps in the adjuvant (ADJ) management. Analysis of available data would lead to perception of the lack of knowledge about management of MBC and would identify areas for future improvement.

Methods

This is a retrospective population based study of all patients with male BC, diagnosed between 2002 and 2013 in Bulgaria. Clinicopathological features and treatment was obtained from the National Cancer Registry. We compare ADJ management in 2 time intervals: 2002-2007 and 2008-2013.

Results

Data about the clinicopathological features of the patients with male BC are shown in Table. Indications for ADJ endocrine treatment (ET), chemotherapy (CHT) or radiotherapy (RT) were considered as per extrapolation for females with BC (Table). Clinicopathological features of patients with male BC, divided in two time intervals. For 2002-2007: Of all 70 nonmetastatic HR+ patients, 10 (14.3%) had ADJ ET; For 2008-2013: Of all 96 nonmetastatic HR+ patients, 36 had ADJ ET (37.5%). For 2002-2007: ADJ RT was delivered to 12 patients of all 70 N+ nonmetastatic male BC (17.1%) For 2008-2013: ADJ RT was delivered to 63 patients of all 94 N+ nonmetastatic male BC (67%) We consider that at least patients with HER+ male BC as well as stages T2-4N+M0 would be indicated for ADJ CHT (73 and 123 for both periods) whereas ADJ CHT was administered to only 9 and 48 patients respectively (12.3 and 39% respectively).

Conclusions

Despite the recommendations to treat male BC as BC in females, use of ADJ modalities, incl. ET, CHT or RT are still largely underused in male BC. There is though a clear trend towards improvement with the years. Data quality of reported cases is improving over time, as well as the staging, diagnosis and ADJ treatment. Despite this, In Bulgaria they remain largely suboptimal and improvement is urgently needed.

Legal entity responsible for the study

Assia Konsoulova.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Table: 98P