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Case Reports in Oncology 2023Metaplastic breast carcinoma (MBC) is a rare histologic subtype of breast carcinoma, which is usually negative for estrogen receptor, progesterone receptor, and HER2....
INTRODUCTION
Metaplastic breast carcinoma (MBC) is a rare histologic subtype of breast carcinoma, which is usually negative for estrogen receptor, progesterone receptor, and HER2. HER2-positive MBC is therefore extremely rare. Most MBCs have poor response to chemotherapy. HER2-targeted neoadjuvant chemotherapy (NAC) is widely performed and has high efficacy in treating HER2-positive breast cancer. We report an atypical case of HER2-positive breast cancer that had poor response to NAC and was diagnosed with MBC after the surgery.
CASE PRESENTATION
A 73-year-old woman noticed a mass in her right breast and visited our hospital. The mass was diagnosed as hormone receptor-negative, HER2-positive invasive ductal carcinoma, T2N0M0 stage IIA. She received HER2-targeted NAC comprising trastuzumab + pertuzumab + docetaxel. Despite three courses, we observed disease progression. The next NAC regimen was composed of two courses of epirubicin + cyclophosphamide, but the cancer continued to grow. She stopped receiving NAC and underwent a unilateral mastectomy and sentinel lymph node biopsy. Although the preoperative pathological result of core needle biopsy specimen showed invasive ductal carcinoma, the postoperative pathological result of the surgical specimen was MBC.
CONCLUSION
In this case, when the patient had undergone three courses of trastuzumab + pertuzumab + docetaxel, it would have been appropriate to review the result of the core needle biopsy with pathologists or to perform vacuum-assisted breast biopsy. This case suggests the importance of considering the possibility of special histologic subtypes such as MBC when a tumor with the diagnosis of invasive ductal carcinoma is resistant to NAC.
PubMed: 38028581
DOI: 10.1159/000534847 -
Immune microenvironment dynamics of HER2 overexpressing breast cancer under dual anti-HER2 blockade.Frontiers in Immunology 2023The clinical prognosis of the HER2-overexpressing (HER2-OE) subtype of breast cancer (BC) is influenced by the immune infiltrate of the tumor. Specifically, monocytic...
INTRODUCTION
The clinical prognosis of the HER2-overexpressing (HER2-OE) subtype of breast cancer (BC) is influenced by the immune infiltrate of the tumor. Specifically, monocytic cells, which are promoters of pro-tumoral immunosuppression, and NK cells, whose basal cytotoxic function may be enhanced with therapeutic antibodies. One of the standards of care for HER2 BC patients includes the combination of the anti-HER2 antibodies trastuzumab and pertuzumab. This dual combination was a breakthrough against trastuzumab resistance; however, this regimen does not yield complete clinical benefit for a large fraction of patients. Further therapy refinement is still hampered by the lack of knowledge on the immune mechanism of action of this antibody-based dual HER2 blockade.
METHODS
To explore how the dual antibody challenge influences the phenotype and function of immune cells infiltrating the HER2-OE BC microenvironment, we developed 3D heterotypic cell models of this subtype. The models comprised aggregates of HER2 BC cell lines and human peripheral blood mononuclear cells. Cells were co-encapsulated in a chemically inert alginate hydrogel and maintained in agitation-based culture system for up to 7 days.
RESULTS
The 3D models of the HER2-OE immune microenvironment retained original BC molecular features; the preservation of the NK cell compartment was achieved upon optimization of culture time and cytokine supplementation. Challenging the models with the standard-of-care combination of trastuzumab and pertuzumab resulted in enhanced immune cytotoxicity compared with trastuzumab alone. Features of the response to therapy within the immune tumor microenvironment were recapitulated, including induction of an immune effector state with NK cell activation, enhanced cell apoptosis and decline of immunosuppressive PD-L1 immune cells.
CONCLUSIONS
This work presents a unique human 3D model for the study of immune effects of anti-HER2 biologicals, which can be used to test novel therapy regimens and improve anti-tumor immune function.
Topics: Humans; Female; Breast Neoplasms; Leukocytes, Mononuclear; Cell Line, Tumor; Trastuzumab; Antineoplastic Agents; Tumor Microenvironment
PubMed: 38022643
DOI: 10.3389/fimmu.2023.1267621 -
Cureus Oct 2023We herein report a case involving a woman with metastatic human epidermal growth factor receptor 2 (HER-2)-positive breast cancer (BC) who became pregnant while...
We herein report a case involving a woman with metastatic human epidermal growth factor receptor 2 (HER-2)-positive breast cancer (BC) who became pregnant while undergoing active anticancer therapy with Trastuzumab-Pertuzumab for her advanced BC disease at our institution. To our knowledge, this is the first reported case of pregnancy and successful delivery in a stage IV BC patient during anticancer therapy. A multidisciplinary approach for such a complex case is a must to evaluate the mother's medical condition by an experienced oncology team along with a maternal-fetal team, with support from a psychiatric and psychological evaluation for the mother. The use of effective contraception during anticancer therapy is essential to avoid such a scenario.
PubMed: 38021854
DOI: 10.7759/cureus.47201 -
Journal For Immunotherapy of Cancer Nov 2023It is possible to induce immunomodulation in HER2-positive breast cancer (BC) by modifying the route of administration of trastuzumab. (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized, open-label, phase II, biomarker study of immune-mediated mechanism of action of neoadjuvant subcutaneous trastuzumab in patients with locally advanced, inflammatory, or early HER2-positive breast cancer-Immun-HER trial (GOIRC-01-2016).
BACKGROUND
It is possible to induce immunomodulation in HER2-positive breast cancer (BC) by modifying the route of administration of trastuzumab.
METHODS
In this multicenter randomized phase II trial, all enrolled patients (pts) with T2-T4d HER2-positive BC received 3 cycles of neoadjuvant treatment (NAT) with fluorouracil, epirubicin and cyclophosphamide every 3 weeks (q21), followed by docetaxel/pertuzumab plus intravenous trastuzumab (arm A) or, docetaxel/pertuzumab plus subcutaneous (SC) trastuzumab (arm B) q21x4 cycles. After surgical operation, each pt was treated with trastuzumab q21x14 cycles using the same SC or intravenous formulation of NAT. Primary endpoint was the proportion of subjects with high stromal tumor-infiltrating lymphocytes (sTILs) in postneoadjuvant residual disease (RD).
RESULTS
Sixty-three pts (31 (arm A) and 32 (arm B)) were enrolled. Pathological complete response was obtained by 20/31 pts (64.5%; 95% CI 45.4% to 80.1%) in arm A and 19/32 pts (59.4%; 95% CI 40.1% to 76.3%) in arm B. High sTILs were observed in 27% and 46% of postneoadjuvant residual tumors in arms A and B, respectively. CD8+ T cells increased significantly in RDs of both arms (p=0.014 and 0.002 for arm A and B, respectively), whereas a significant decline in the level of CD4+ FoxP3+ regulatory T cells was observed only in arm B (p=0.016). A significant upregulation of PD-1 on sTILs was found in RD of pts enrolled in arm B (p=0.012), while programmed death-ligand 1 (PD-L1) was significantly overexpressed in residual tumors of arm A (p=0.02). A strong negative correlation was reported in arm B between expression of PD-L1 on pretreatment sTILs and CD3 expression on sTILs in RD (τ: -0.73). Grade≥3 AE incidence rates were similar between the two arms.
CONCLUSIONS
SC trastuzumab induced relevant sTILs enrichment, with favorable variations of immune parameters in HER2-positive BC pts with RD after NAT. Novel immunotherapy strategies should be tested to achieve SC-specific, antitumor immune response.
TRIAL REGISTRATION NUMBER
NCT03144947, and EudraCT number: 2016-000435-41.
Topics: Humans; Female; Trastuzumab; Breast Neoplasms; B7-H1 Antigen; Docetaxel; Neoadjuvant Therapy; Neoplasm, Residual; Receptor, ErbB-2; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38016718
DOI: 10.1136/jitc-2023-007667 -
Oral Oncology Jan 2024Salivary gland cancers (SGCs) are a heterogeneous group of rare tumors including various histological subtypes with different molecular profiling. Human epidermal growth... (Review)
Review
Salivary gland cancers (SGCs) are a heterogeneous group of rare tumors including various histological subtypes with different molecular profiling. Human epidermal growth factor receptor 2 (HER2) is one of the most intriguing and studied molecular alterations with prognostic and predictive roles. Indeed, HER2 overexpression is commonly correlated with aggressive histological subtypes and poorer prognosis. However, HER2 may represent the target of personalized treatment. We performed a literature review of use of anti-HER2 targeted agents for treatment of recurrent or metastatic SGCs. The efficacy and safety of anti-HER2 were firstly evaluated in patients affected with other solid tumors, mostly breast and gastric cancers. For SGCs the literature is mainly comprised of case reports or case series and small clinical trials. The most common used drug is trastuzumab in combination with chemotherapy (i.e. taxanes, capecitabine, carboplatin, eribulin) or with another anti-HER2 targeted agent (i.e. pertuzumab). The use of anti-HER2 therapies induces improvement in clinical responses, which are mostly durable. Besides, new anti-HER2 drugs such as antibody-drug conjugates (ADC) (i.e. trastuzumab emtansine, trastuzumab deruxtecan) have been introduced in this setting inducing further therapeutic advances. Anti-HER2 treatment strategy is emerging as potentially effective in selected HER2 overexpressing SGCs. However, prospective and multicentric clinical trials are needed to evaluate the efficacy of these therapeutic regimens within larger cohorts and to assess the most appropriate treatment sequence strategy.
Topics: Female; Humans; Ado-Trastuzumab Emtansine; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Carboplatin; Prospective Studies; Salivary Gland Neoplasms
PubMed: 38016228
DOI: 10.1016/j.oraloncology.2023.106612 -
Breast (Edinburgh, Scotland) Feb 2024• 101 patients with HER2+ MBC on pertuzumab and trastuzumab were included. • Most observed cardiotoxicity were mild, all occurred early within 24 months. •...
• 101 patients with HER2+ MBC on pertuzumab and trastuzumab were included. • Most observed cardiotoxicity were mild, all occurred early within 24 months. • Presence of cardiovascular co-morbidities predicts treatment cardiotoxicity. • Risk-stratified de-escalation of long-term cardiac surveillance should be discussed.
Topics: Humans; Female; Breast Neoplasms; Receptor, ErbB-2; Trastuzumab; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38007881
DOI: 10.1016/j.breast.2023.103612 -
Clinical Breast Cancer Feb 2024This study aims to explore whether first-line pertuzumab use modifies the effect of prior use of (neo-) adjuvant trastuzumab on the PFS of first-line HER2-targeted...
BACKGROUND
This study aims to explore whether first-line pertuzumab use modifies the effect of prior use of (neo-) adjuvant trastuzumab on the PFS of first-line HER2-targeted therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC).
METHODS
Patients diagnosed with HER2-positive ABC in 2008 to 2018 in 9 Dutch hospitals were derived from the SONABRE Registry (NCT03577197). Patients diagnosed with de novo metastatic breast cancer were excluded. Patients receiving first-line trastuzumab-based therapy for ABC were selected and divided into trastuzumab naïve (n = 113) and trastuzumab pretreated (n = 112). Progression-free survival (PFS) was compared using multivariable Cox proportional hazard models. The interaction effect of first-line pertuzumab was tested using the likelihood-ratio test.
RESULTS
The median follow-up time was 47 months (95% confidence interval [CI]: 42-52). When comparing trastuzumab pretreated with trastuzumab naïve patients, the hazard ratio for first-line progression was 2.07 (CI:1.47-2.92). For trastuzumab pretreated patients who received first-line trastuzumab without pertuzumab, the hazard ratio for progression was 2.60 (95% CI:1.72-3.93), whereas for those who received first-line trastuzumab with pertuzumab the hazard ratio was 1.43 (95% CI: 0.81-2.52) (P interaction = .10).
CONCLUSIONS
Prior use of trastuzumab as (neo-)adjuvant treatment had a negative impact on PFS of first-line HER2-targeted therapy outcomes. Adding pertuzumab to first-line trastuzumab-based therapy decreased the negative impact of prior (neo-)adjuvant trastuzumab use on first-line PFS. Further studies are needed to assess the effect of prior (neo-)adjuvant pertuzumab use on the outcomes of first-line pertuzumab-based therapy.
Topics: Humans; Female; Trastuzumab; Breast Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Receptor, ErbB-2; Progression-Free Survival; Proportional Hazards Models
PubMed: 38007349
DOI: 10.1016/j.clbc.2023.10.009 -
Cancer Treatment and Research... 2023Trastuzumab emtansine (T-DM1) significantly improves invasive disease-free survival and reduces the risk of recurrence in patients with HER2-positive early breast cancer...
Real world data on the demographic and clinicopathological profile and management of patients with early-stage HER2-positive breast cancer and residual disease treated with adjuvant trastuzumab emtansine (KARMA study).
INTRODUCTION
Trastuzumab emtansine (T-DM1) significantly improves invasive disease-free survival and reduces the risk of recurrence in patients with HER2-positive early breast cancer (EBC) with residual disease (RD). The KARMA study aimed to describe the characteristics and management of these patients in clinical practice in Spain.
MATERIAL AND METHODS
We conducted a multicentre retrospective study in patients with HER2-positive EBC with RD following neoadjuvant treatment (NeoT) and who had received ≥1 dose of T-DM1 as adjuvant treatment. The primary endpoint was the evaluation of sociodemographic and clinicopathological characteristics of these patients.
RESULTS
A total of 114 patients were included (March-July 2020). At diagnosis, most tumours were infiltrating ductal carcinoma (IDC) (93.9 %), grade 2 (56.1 %), and hormone receptor (HR)-positive (79.8 %). Over 75 % of patients had disease in operable clinical stages (T1-3 N0-1). In the neoadjuvant setting, 86.8 % of patients received trastuzumab plus pertuzumab, and 23.6 % achieved radiological complete response. Breast-conserving surgery was performed in 55.8 % of patients. Surgical specimens showed that 89.5 % of patients had IDC, 49.1 % grade 2, 84.1 % HR-positive, and 8.3 % HER2-negative disease. Most patients had RD classified as RCB-II and Miller/Payne grade 3/4. Grade 3 treatment-related adverse events (trAEs) occurred in 5.3 % of patients. No grade 4/5 AEs occurred. Over 95 % of patients were free of invasive-disease during T-DM1 adjuvant treatment.
CONCLUSION
The KARMA study describes the characteristics of patients with HER2-positive EBC with RD after NeoT and the real-life management of a T-DM1 adjuvant regimen, which showed a manageable safety profile in line with the KATHERINE trial data.
Topics: Humans; Female; Ado-Trastuzumab Emtansine; Breast Neoplasms; Retrospective Studies; Receptor, ErbB-2; Maytansine; Antineoplastic Combined Chemotherapy Protocols; Demography
PubMed: 37995519
DOI: 10.1016/j.ctarc.2023.100772 -
NPJ Breast Cancer Nov 2023The PATRICIA study (NCT02536339) examined the efficacy and safety of pertuzumab plus high-dose trastuzumab in patients with HER2-positive metastatic breast cancer (MBC)...
The PATRICIA study (NCT02536339) examined the efficacy and safety of pertuzumab plus high-dose trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) with progressive central nervous system (CNS) metastases following radiotherapy. Primary analysis confirmed CNS objective response rate (ORR) was 11% (95% confidence interval [CI]: 3-25); clinical benefit rate (CBR) was 68% (4 months) and 51% (6 months). We report final efficacy data after a further 21-months of follow-up, updated safety, survival, and patient-reported outcomes (PROs). Patients received standard-dose pertuzumab plus high-dose trastuzumab (6 mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity. Primary endpoint: confirmed ORR (CNS) per Response Assessment in Neuro-Oncology Brain Metastases criteria. Secondary endpoints were response duration, CBR, progression-free survival (PFS), overall survival (OS), safety, and PROs. By clinical cut-off, 39 patients had completed or discontinued treatment. Confirmed ORR (CNS) was 11% (95% CI: 3.0-25.4). Median CNS-PFS was 4.6 months (95% CI: 4.0-8.9), as was median CNS-PFS or systemic PFS (95% CI: 4.0-8.9); median OS was 27.2 months (95% CI: 16.1-not reached). CBR in the CNS was 51% (19 patients, 95% CI: 34.4-68.1) at 6 months. Two patients remained on treatment until study closure, achieving stable disease for 4.1 and 4.8 years. Treatment-related grade 3/4 adverse events occurred in 7.7% of patients. Patients with confirmed partial response or stable disease (≥4 months) in the CNS had stable PROs over time. Pertuzumab plus high-dose trastuzumab represents a reasonable non-chemotherapeutic treatment option for selected patients with HER2-positive MBC with CNS metastases.
PubMed: 37978197
DOI: 10.1038/s41523-023-00587-2