Aim. To examine the clinical management of metaplastic breast cancer (MeBC), particularly the role of chemotherapy. Methods. This retrospective study included patients with MeBC (n = 73) from a ...tertiary breast cancer center: the “Centre des Maladies du Sein of the CHU de Québec–Université Laval.” The specimens were reviewed by two pathologists. Patient and tumor characteristics, systemic therapy (neoadjuvant and adjuvant), disease-free survival (DFS), and overall survival (OS) were recorded. Results. The median follow-up was 57.2 months. The mean tumor size was 39.5 ± 32.1 (range, 1–200) mm. Most were in grade 3 (75.3%), without evidence of clinical nodal involvement (75.3%), and triple-negative (79.5%). Chemotherapy was given to 49 (67.1%) patients. Thirty-seven patients (50.7%) underwent a mastectomy, and 22/37 (59.5%) received radiotherapy. Adjuvant chemotherapy was given to 36 patients (49.3%), and nine (12.3%) patients were treated with neoadjuvant chemotherapy. The 5-year OS and DFS rates were 60.2% and 66.8%. Among the nine patients who received neoadjuvant chemotherapy, three (33.3%) achieved a partial response, three (33.3%) had stable disease, and three (33.3%) had disease progression. The use of chemotherapy, especially in the adjuvant setting, had a significant positive effect on 5-year OS (P=0.003) and 5-year DFS (P=0.004). Nodal involvement was associated with worse OS (P=0.049) but similar DFS (P=0.157). Lumpectomy was associated with better 5-year OS (P<0.0001) and DFS (P=0.0002) compared with mastectomy. Conclusion. MeBC represents a rare heterogeneous group of malignancies with poor prognosis. Adjuvant chemotherapy was associated with improved OS and DFS. Patients should be carefully selected for neoadjuvant chemotherapy.
This study investigated if fear of cancer recurrence (FCR) levels and the proportion of women having a clinical level of FCR differed by whether women had or had not experienced disruptions in their ...cancer tests and treatments due to the pandemic.
We conducted a mixed-methods study between November 2020 and March 2021 among women diagnosed with breast cancer in the previous five years at the time of their entry in the study. Women completed a questionnaire online assessing disruptions in breast cancer tests and treatments due to the pandemic and the severity subscale of the Fear of Cancer Recurrence Inventory. Semi-structured interviews were also conducted with a subsample of 24 participants and were thematically analyzed.
The proportion of patients with a clinical level of FCR was significantly higher among those who experienced the postponement or cancellation of diagnostic and disease progression tests (e.g., blood tests, X-rays, or magnetic resonance imaging; adjusted PR = 1.27 95% CI = 1.13-1.43). Qualitative findings suggest that FCR was exacerbated by the pandemic context. In particular, perceived or actual barriers to care access due to the pandemic were identified as significant FCR-enhancing factors.
These results highlight the need to keep diagnostic and progression tests as timely as possible to prevent increases in FCR levels and offer counselling about FCR when postponing or cancellation are inevitable.
Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a ...collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants’ understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics.
Background: Generic formulations are not necessarily identical to the original in terms of efficacy and adverse events. Generic docetaxel has been available in Canada since 2011. Objective: To ...compare the occurrence of grade III to IV adverse events between original docetaxel and a generic formulation in breast cancer patients. Methods: A consecutive series of 400 patients were assessed retrospectively: 200 who received the original docetaxel and 200 who received a generic formulation. Patients who received both formulations or received their chemotherapy outside our center were excluded. The primary outcome was the occurrence of grade III to IV adverse events related to docetaxel (febrile neutropenia, hand and foot syndrome, intestinal perforation, thrombotic event, and death). Results: Three hundred-sixty-four patients were available for analysis (182/group). The use of a granulocyte colony-stimulating factor (G-CSF) was more frequent in the generic group (44.5% vs 28.8%), as well as treatment discontinuation (26.4% vs 14.8%). The occurrence of grade III to IV febrile neutropenia, hand and foot syndrome, intestinal perforation, thrombotic event, and docetaxel-related deaths were similar between the 2 formulations. However, grade IV febrile neutropenia was more frequent with the generic formulation (78.8% vs 56.3%). Limitations were the retrospective nature of the study and the variety of chemotherapy regimens. Conclusion: Adverse events occurrence was similar between the 2 formulations. However, febrile neutropenia was more serious with generic docetaxel, despite increased G-CSF use. Results suggest that the studied generic formulation may be safe, but more caution during treatments might be warranted, especially concerning febrile neutropenia events.
Abstract
Introduction: Multiple HER2-targeted therapies are now available and have significantly altered the natural course of HER2-positive metastatic breast cancer (mBC), with overall survival (OS) ...now exceeding 4 years. However, patients with HER2-positive mBC represent a heterogeneous population with some patients presenting with a history of a localized cancer and some with de novo metastatic disease. Our aim was to study the outcomes of HER-positive mBC in a real-life setting and compare the evolution between patients with “recurrent” breast cancer compared to those with “de novo” disease. Methods: In this single-center, retrospective study, we included patients with HER2-positive mBC treated at the Centre hospitalier universitaire (CHU) de Quebec using the local cancer registry and patients’ medical charts. We included all female patients > 18 years of age who received one or more anti-HER2 therapy for mBC. Patients whose follow-up at our center was incomplete were excluded. We identified patients who developed mBC after the occurrence of a localised disease (“Recurrent” group) and patients diagnosed with metastatic disease upon first presentation (“De novo” group). Primary outcome was OS. Secondary outcomes were progression-free survival (PFS) for each line of treatment and for each type of treatment (trastuzumab T, pertuzumab P, lapatinib L and trastuzumab emtansine T-DM1). We performed survival analysis using the Kaplan-Meier method and the log rank test. Results: A total of 106 patients in the Recurrent group and 58 patients in the De novo group were identified between May 2002 and December 2018 and data were collected between March and June 2019, by which time 97 (59.1%) had died. There were differences in baseline characteristics between the Recurrent and the De novo groups regarding age at first metastasis (50.7 vs 57.4 years, p=0.001). A total of 44.3 % vs 32.8 % of patients developed brain metastasis respectively (p=0.15). There was no statistical difference between the two groups regarding OS (3.8 years for Recurrent vs 4.2 years for De novo, p=0.17). PFS were also similar between the 2 groups for every anti-HER2 treatment available during the study period (Table 1). Median PFS could not be established for P in the De novo group since 80 % of patients were censured at the time of data collection. In the Recurrent group, P, L and T-DM1 had median PFS at least as long as those reported in landmark clinical trials. PFS were also similar between groups when comparing treatment lines (Table 2). Conclusion: In this retrospective study of patients from a real-world setting, anti-HER2 therapies offered similar OS between HER2-positive mBC patients with recurrent disease and with de novo metastatic disease. Median PFS are also equivalent between groups, with durations in the range of the PFS reported in major RCTs.
Table 1TreatmentRecurrent groupRecurrent groupDe novo groupDe novo groupP valuenMedian PFS (years)nMedian PFS (years)Trastuzumab741.7441.90.14Pertuzumab333.115-0.15Lapatinib290.7110.60.17T-DM1310.7120.70.52
Table 2LineRecurrent groupRecurrent groupDe novo groupDe novo groupP valuenMedian PFS (years)nMedian PFS (years)1sd1061.6582.00.142nd490.7200.60.273rd230.990.70.794th100.430.80.53
Citation Format: Vincent Douville, Christine Desbiens, Valérie Théberge, Caty Blanchette, Julie Lemieux. Real-world experience of patients treated for HER2-positive metastatic breast cancer at the centre hospitalier universitaire de Quebec: A retrospective cohort study abstract. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-37.
ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in ...women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings.
In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1–3c (modified to stage 2–3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1–3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants.
Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1–5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57–0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3–91·8) in the neratinib group and 87·7% (85·7–89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3–4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 40% grade 3 and one <1% grade 4 with neratinib vs 23 2% grade 3 with placebo), vomiting (grade 3: 47 3% vs five <1%), and nausea (grade 3: 26 2% vs two <1%). Treatment-emergent serious adverse events occurred in 103 (7%) women in the neratinib group and 85 (6%) women in the placebo group. No evidence of increased risk of long-term toxicity or long-term adverse consequences of neratinib-associated diarrhoea were identified with neratinib compared with placebo.
At the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses—ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast—without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events.
Wyeth, Pfizer, and Puma Biotechnology.
Background. Primary breast angiosarcoma is a rare entity. Case. Initial diagnosis was a benign hemangioma at core biopsy. Wide local excision was performed, with positive margins. Pathology after ...surgery reported a moderately differentiated angiosarcoma. Tumor was finally treated using mastectomy and radiations. She developed a second angiosarcoma in contralateral breast, with an initial diagnosis on core biopsy of an atypical vascular lesion and was again treated using mastectomy and radiations. She developed bones and lung metastases. Conclusion. Primary breast angiosarcoma is a rare entity often difficult to diagnose on core biopsy, and a benign differential diagnosis is frequent. A highly vascular breast mass should always be considered malignant until proven otherwise. Surgical treatment seems to be the best course of action. There is a lack of data proving efficacy of adjuvant chemotherapy and radiation therapy.
The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with ...pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety.
One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015.
With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome.
With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.
•Adjuvant olaparib versus placebo significantly improved OS in gBRCA1/2pv-associated human epidermal growth factor receptor 2-negative EBC (4-year OS 90% versus 86%).•Adjuvant olaparib versus placebo improved 4-year IDFS (83% versus 75%) and 4-year DDFS (87% versus 79%).•Adjuvant olaparib demonstrated benefit across major subgroups for OS, IDFS, and DDFS, including by hormone receptor status.•With 3.5 years of median follow-up there were two acute myeloid leukemia/myelodysplastic syndrome cases (0.2%) with olaparib and three (0.3%) with placebo.•With 1-year of additional follow-up, no new safety signals were identified with adjuvant olaparib compared to placebo.
Abstract
Background: Metaplastic breast cancer (MeBC) is a rare subtype accounting for 0.2%-5% of all invasive breast cancer. They are characterized by an aggressive course and even a worse prognosis ...than triple-negative breast cancer (TNBC). The literature suggests that MeBCs are relatively chemoresistant; still, the patients often receive adjuvant or neoadjuvant chemotherapy during the course of treatment. This study aimed to examine the clinical management of MeBC, particularly the role of chemotherapy. Methods: This retrospective study included patients with MeBC (n=73) from the Centre des Maladies du Sein du CHU de Québec-Université Laval. The specimens were reviewed by two pathologists. Patient and tumor characteristics, systemic therapy (neoadjuvant and adjuvant), disease-free survival (DFS), and overall survival (OS) were recorded. Results: The median follow-up was 57.2 months. The mean tumor size was 39.5±32.1 (range, 1-200) mm. The vast majority had grade 3 (76.7%), no evidence of clinical nodal involvement (78.1%), and triple-negative (79.5%) disease. This population included one case (1.4%) of low-grade adenosquamous breast carcinoma, one (1.4%) of fibromatosis-like metaplastic carcinoma, 11 (15.1%) of spindle cell carcinoma, 13 (17.8%) of epidermoid carcinoma, 18 (24.7%) of MeBC with heterologous mesenchymal differentiation, and 29 (39.7%) of mixed MeBC. Chemotherapy was given to 53 (72.6%) patients. Thirty-seven patients (50.7%) had a lumpectomy, and 34/37 (91.9%) received adjuvant radiotherapy. Thirty-six patients (49.3%) had mastectomy and 22/36 (61.1%) received radiotherapy. The 5-year DFS was 55.6%, and the 5-year OS was 63.5 %. On univariable analyses, higher cT stage (cT3-4) was associated with poorer DFS and OS compared to cT1-2, respectively 13.4% vs. 70.7% (P<0.0001) and 19.9% vs. 82.8% (P<0.0001). Nodal involvement significantly influenced DFS (31.3% vs. 63.0%, P=0.011) and OS (37.5% vs. 71.6%; P=0.009). Lumpectomy was associated with a better 5-year DFS (78.4% vs. 34.0%, P<0.0001) and OS (90.6% vs. 38.8%, P<0.0001). The use of chemotherapy had a significant positive effect on 5-year DFS (64.2% vs. 31.9%, P=0.006; hazard ratio (HR)=0.45, 95% confidence interval (CI)=0.22-0.92, P=0.009) as well as 5-year OS (69.7% vs. 45.1%, P=0.035; HR=0.52, 95%CI=0.28-0.95 P=0.041). However, radiation therapy did not influence DFS (P=0.420) and OS (P=0.316). Nine patients received neoadjuvant chemotherapy; five had nodal involvement. One patient had a complete response (11.1%), five (55.6%) had a partial response, and three (33%) had progressive disease. The 5-year DFS and OS were lower for neoadjuvant chemotherapy compared with adjuvant chemotherapy (DFS: 27.8% vs. 71.5%, P=0.006; OS: 33.3% vs. 79.2%, P=0.001), but disease was more advanced in patients with neoadjuvant chemotherapy (cT3-4: 88.9% vs. 11.9%, P<0.0001). Conclusion: MeBC represents a rare heterogeneous group of malignancies with poor prognosis. Chemotherapy was associated with improved DFS and OS. Patients for neoadjuvant chemotherapy should be carefully selected.
Citation Format: Kassandra J Thériault, Mariem Ben Moussa, Marjorie Perron, Christine Desbiens, Brigitte Poirier, Éric Poirier, Dominique Leblanc, Claudya Morin, Julie Lemieux, Jean-Charles Hogue, Dominique Boudreau. Metaplastic carcinoma of the breast: A single-center 18-year series of 73 cases abstract. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-12-03.
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