Abstract
Background: Trastuzumab (Herceptin®; H) is a standard component of adjuvant treatment in patients with HER2+ early breast cancer (eBC) and is supported by all major treatment guidelines. The ...efficacy and safety of Herceptin intravenous (H IV) and Herceptin subcutaneous (H SC) have been shown to be comparable. The main advantage of SC administration is its shorter administration time. Administration at home for selected patients will allow greater independence and may lead to an improved quality of life. In this study, we assessed the safety and tolerability of H SC administered at home by a healthcare professional (HCP) in patients with HER2+ eBC.
Methods: Patients with HER2+ eBC who previously completed 6 cycles of H IV could be included in the study to receive 12 additional cycles of H for a total of 18 cycles. The 12 additional 3-week cycles consisted of 3 cycles of H IV in the hospital (6 mg/kg; cycles 7 to 9; period 1); 3 cycles of H SC in the hospital (600 mg; cycles 10 to 12; period 2); and 6 cycles of H SC administered in the home by a HCP (600 mg; cycles 13 to 18; period 3). Patients are being followed for a total of 24 months after their last treatment. Safety is being assessed from the adverse events (AEs) reported during the study. Patient-reported outcomes were obtained from validated questionnaires for: the satisfaction and quality of the treatments and care, and for symptom severity (0 absent to 10 worst). HCPs also reported on their experiences with both treatments.
Results: A total of 102 patients were treated in the study between November 2013 and July 2015 and will be followed for safety and efficacy through July 2017. The primary analysis reported here was done after the last 4-week post-treatment follow-up was completed (September 2015). Patient mean age at baseline was 54.4±12.3 (SD) years. A total of 91 (89%) patients reported 549 AEs: 535 (97%) of these were grade 1 or 2 and 194 (35%) were considered treatment related. The proportions of patients with at least one related AE were 7% for H IV period 1, 32% for H SC period 2, and 47% for H SC period 3, which was twice as long as periods 1 or 2. A total of 8 serious AEs were reported in 8 patients (2 each in periods 1 and 2; 4 in period 3). Prior to the first at-home SC administration (cycle 13), 99% of patients were satisfied to a large or very large extent with the IV and SC treatments at the hospital. At cycle 17, 100% of patients were satisfied to a large or very large extent with the SC treatment at home, and 100% of patients thought treatment at home was beneficial to a large or very large extent. In all 3 treatment periods, maximum mean scores were 3.0−3.8 for the most severe symptoms (fatigue, disturbed sleep, and numbness or tingling). All HCPs considered both administration routes to be fairly easy or very easy, and SC administration to be quicker and require fewer preparation resources.
Conclusions: The safety analyses and patient-reported outcomes recorded in this study indicate that H SC administered by a HCP at home instead of at the hospital was not associated with any new safety signals and was considered beneficial by the patients and HCPs.
Citation Format: Cocquyt VF, Martinez-Mena CL, Martens MT, D'Hondt RG, Graas M-PL, Evron E, Fried G, Ben-Baruch NE, Dijkstra AC, Van De Walle EI. BELIS: Safety and tolerability of at home administration of trastuzumab (Herceptin®) subcutaneous for the treatment of patients with HER2-positive early breast cancer abstract. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-17.
Aim: Preoperative chemotherapy (PCT) is used in primary breast cancer, to facilitate breast conservative surgery (BCS). Clinical and pathologic responses are important prognostic parameters. Biologic ...markers are needed to individualize treatment.
Patients and Methods: One hundred and thirty-five patients with breast carcinoma were treated with PCT, followed by surgery and adjuvant therapy. Clinical response and pathological complete response (pCR), biological markers and type of surgery were compared between invasive ductal (IDC) and invasive lobular carcinoma (ILC).
Results: Overall response (OR) for IDC was 75% compared to 50% for ILC (P=0.0151). Pathological CR was 15% for IDC and 0% for ILC (P=0.0066). Fifty-six percent of the responding patients had BCS, in contrast with 16% of the non-responders. BCS was performed in 50% of patients with IDC, in 38% of the patients with ILC. Salvage surgery was more necessary in ILC (19%) compared to IDC (4%) (P=0.0068). Patients with ILC were more frequently ER-positive and HER-2 negative than patients with IDC.
Conclusions: Clinical and pathological responses are lower in ILC compared to IDC. After PCT, patients with large ILC should preferably be offered mastectomy with immediate breast reconstruction. However, PCT still remains valuable to evaluate tumor response and biologic factors in vivo.
Preoperative chemotherapy (PCT) can be used in large primary breast cancer to facilitate breast conservative surgery (BCS). Cosmetic results of BCS are influenced by the size of the residual tumour, ...relative to the size of the breast. After mastectomy, immediate breast reconstruction (IBR) with autologous tissue provides excellent cosmetic outcome and has proven to be safe in breast cancer patients. Besides improving overall and disease free survival, Quality of Life (QoL), body image and cosmetic outcome are also important issues after treatment for breast cancer.
In this study, Health-Related-Quality of Life (HRQL) and body image were evaluated, in patients treated with PCT, followed by BCS, or skin-sparing mastectomy (SSM) and perforator-flap breast reconstruction. Additionally, clinical observers assessed cosmetic outcome.
All participants were evaluated by the Medical Outcomes Study (MOS) 36-item Short Form Health Status Survey (SF-36, 36 items) and a study-specific questionnaire. An external panel evaluated standardised photographs of the breasts.
For all patients, norm-based scores of physical and mental health state are comparable with the general population, except for vitality (VT) score, which is somewhat lower. No significant differences can be observed between both groups. The majority of the patients were satisfied with the appearance of their breasts.
The cosmetic results, assessed by the clinical team, were significantly better for patients having IBR, compared to BCS. The mean score was 7.5/10 for IBR, versus 6.0/10 for BCS (
p<0.0001).
Breast conserving treatment or mastectomy with reconstruction may yield comparable results of QoL, but cosmetic outcome is better after SSM and perforator-flap reconstruction. Patients must be offered both options, and clinicians should stress that both are equally effective.
The aim of this prospective study was to evaluate biological markers, their correlation with response and outcome, and the change in these markers under the influence of preoperative chemotherapy ...(PCT) in patients with a large primary breast cancer. One hundred and thirty-five women were treated with PCT, followed by locoregional therapy and adjuvant treatment. Estrogen receptor (ER), progesterone receptor (PgR), HER-2, p53, and cathepsin D were determined by immunohistochemistry (IHC) before and after PCT. The overall response (OR) was 70% and the pathologic complete response (pCR) was 13%. Forty-four percent of the patients could be offered breast-conserving surgery (BCS). At a median follow-up of 50 mo the overall survival is 82% and the disease-free survival is 70%. No local recurrence (LR) has developed following BCS. Invasive ductal carcinoma (IDC) was more frequently ER-negative and HER-2-positive than invasive lobular carcinoma (ILC). P53-negative and ER-negative patients seemed to be more chemosensitive compared to p53-positive patients (74% vs 53%) and ER-positive patients (75% vs 65%), but this difference did not reach statistical significance. A trend toward higher complete pathologic remission rate was seen for ER-negative patients (p = 0.0609). PgR, HER-2, and cathepsin D were not related to response. The pattern of biological markers did not change with PCT, making repeated determination useless.
The response to preoperative chemotherapy in breast cancer was assessed by magnetic resonance imaging (MRI), and compared to the histological and clinical findings.
Forty-two patients with stage II ...and III breast carcinoma were evaluated prospectively prior to and after preoperative chemotherapy by MRI, clinical and histological examination. Radiological response was assessed using the MRI parameters: total tumor volume (TTV), maximum enhancement index (MEI) and their product (TTV
*MEI).
A significant reduction in all MRI parameters was observed after chemotherapy. Overall clinical and radiological response rates were comparable (69% vs 73%). MRI was not useful for the prediction of complete pathologic response. A fair correlation between TTV postchemotherapy and final histological diameter was found. A significant difference of residual TTV for patients undergoing breast conservative surgery vs mastectomy was observed.
Conclusion: MRI can demonstrate responses induced by preoperative chemotherapy in breast cancer, but it cannot determine complete pathologic responses.
PDF
