HER2 Positive Breast Cancer:…Invasive Breast Cancer…HER2-Positive Preferred Regimens…TCH+pertuzumab…Docetaxel 75mg/m2 IV day 1…Carboplatin AUC 6 IV day 1…Cycled every 21 days for 6 cycles…with…Trastuzumab 8mg/kg IV day 1…Pertuzumab 840 mg IV day 1…followed by Trastuzumab 6mg/kg IV on day 1...Pertuzumab 420mg IV on day 1...

A pertuzumab-containing regimen may be administered preoperatively to patients with greater than or equal to T2 or greater than or equal to N1, HER2-positive early-stage breast cancer.

In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not...In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality...

Pertuzumab retreatment in patients with HER2-positive locally advanced/metastatic breast cancer...At the data cutoff (Dec 31, 2021), OS and PFS events were 138 (63.6%) and 190 (87.6%), respectively. Updated median OS was significantly longer in the PTC group (median OS 36.2 vs. 26.5 mo.; HR = 0.73 [one side 95%CI upper limit, 0.97]; log-rank test p = 0.0323).

Pertuzumab use improved pCR rates (65% vs 41%, adjusted odds ratio [aOR] 3.01; 95% confidence interval [CI] 2.29-3.97; p<0.001)….the efficacy of pertuzumab to achieve a pCR in stage II and III HER2-positive breast cancer...

...ER/PR positive is defined as >1% stained cells and HER2-positive is defined as IHC 3+ or in-situ hybridisation (ISH) ratio >2.0....

...• Signed Informed Consent Form• Age ≥ 18 years• Eastern Cooperative Oncology Group (ECOG) Performance Status 0−2• Histologically documented breast cancer• Locally advanced or metastatic breast cancer that has progressed on the patient's most recent prior regimen - For the purposes of this study, locally advanced breast cancer is defined as unresectable local or regional disease that has previously been treated with radiation therapy, chemotherapy, and HER2-directed therapy.• HER2-positive breast cancer documented as fluorescence in situ hybridization (FISH)-positive, immunohistochemistry (IHC) 3 + or chromogenic in situ hybridization (CISH)-positive by local laboratory assessment• Tumor tissue blocks or 15−20 unstained tissue slides for confirmatory centrallaboratory HER2 status testing and other exploratory assessments• Prior trastuzumab in any line of therapy• Prior chemotherapy combined with HER2-targeted therapy for locally advanced or metastatic disease• No prior T-DM1 or pertuzumab therapy• Measurable disease, defined as at least one lesion ≥ 2 cm on computed tomography (CT) scan or ≥ 1 cm on spiral CT scan• Cardiac ejection fraction ≥ 55% by either ECHO or MUGA scan • Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to first study treatment: - Absolute neutrophil count ≥ 1500 cells/mm3 - Platelet count ≥ 100,000 cells/mm3 - Hemoglobin ≥ 9.0 g/dL - Albumin ≥ 2.5 g/dL - Total bilirubin ≤ 1.5 × ULN - SGOT (AST) and SGPT (ALT) ≤ 2.5 × ULN, with the following exception: Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN - Serum creatinine ≤ 1.5 mg/dL, or creatinine clearance ≥ 50 mL/min based on Cockroft-Gault glomerular filtration rate (GFR) estimation: - (140 − age) × (weight in kg) × (0.85 if female)/72 × serum creatinine• For women of childbearing potential, agreement to use an effective form of contraception (patient and/or partner [e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants]), and to continue its use for the duration of the study• Life expectancy ≥ 90 days`• Signed Informed Consent Form• Age ≥ 18 years• Eastern Cooperative Oncology Group (ECOG) Performance Status 0−2• Histologically documented breast cancer• Locally advanced or metastatic breast cancer- For the purposes of this study, locally advanced breast cancer is defined as unresectable local or regional disease.• HER2-positive breast cancer documented as fluorescence in situ hybridization (FISH)-positive, immunohistochemistry (IHC) 3 + or chromogenic in situ hybridization (CISH)-positive by local laboratory assessment• Confirmed availability (prior Day 1) of tumor tissue blocks or 15−20 unstained tissue slides at screening for confirmatory central laboratory HER2 status testing and other exploratory assessments. ...

...- Biopsy proven HER2-positive or HER2-low primary malignancy or metastatic disease...

...Allowed previous and concomitant bisphosphonates/denosumab - Età >18 anni- Diagnosi istologica di carcinoma mammario avanzato HER2-positivo;- Precedente trattamento con pertuzumab per malattia metastatica;- Performance status ECOG 0-2; - Adeguata funzionalità d’organo, definita come: neutrofili =1,5x109/l; conta piastrinica = 100x109/l; emoglobina =10g/dL; creatinina =1,5x limite superiore normale (UNL), bilirubina sierica totale =1,5xUNL; alanina aminotransferasi (ALT), aspartato aminotransferasi (AST) =2.5xUNL; fosfatasi alcalina (AP) = 2.5xUNL; se la fosfatasi alcalina totale (AP)> 2.5xUNL, la frazione epatica di fosfatasi alcalina deve essere =2.5xUNL; frazione di eiezione ventricolare sinistra (LVEF) =50% misurata nei 28 giorni precedenti la prima somministrazione del trattamento in studio, determinata dall'ecocardiografia (ECHO) o dalla scintigrafia miocardica (MUGA);- Malattia misurabile;- Risoluzione delle eventuali tossicità correlate al trattamento precedente, che devono essere = Grado 1 al momento della randomizzazione; - Contraccezione adeguata per tutti i pazienti fertili- Test di gravidanza negativo; - Sono ammessi trattamenti precedenti e/o concomitanti con bifosfonati/denosumab;- Consenso informato scritto....

...Patients must meet the following criteria for study entry:-Have signed the informed consent -Age more than or equal with 18 years at time of signing Informed Consent Form;-Female patients with HER-2 positive advanced breast cancer, locally unresectable or metastatic breast cancer;-Ability to comply with the study protocol;-Eastern Cooperative Oncology Group (ECOG) Performance Status should be 0-1;-Good patient adherence;-Indication: histologically and by imaging confirmed HER-2 positive metastatic advanced breast cancer;-No contraindication of trastuzumab and pertuzumab treatment;-Finished preliminary combined chemotherapy cycles with pertuzumab and trastuzumab for breast cancer;-Life expectancy is more than 6 months;-Baseline LVEF is more than 50% measured by echocardiography (ECHO);-A negative serum pregnancy test for premenopausal female objects must be available prior to enrolment, unless they have undergone surgical sterilization (removal of ovaries and/or uterus)....

...- Histologically confirmed Patients ≥ 18 years-old with non-operable, locally advanced, or metastatic HER-2 positive breast cancer Docetaxel, Paclitaxel or Vinorelbine-based chemotherapy administred in combination with any trastuzumab biosimilar and with pertuzumab for the first-line treatment of the non-operable, locally advanced or metastatic HER-2 positive breast cancer....

...A confirmed HER2-positive status assessed by means of immunohistochemical analysis (with 3+ indicating positive status) and/or in situ hybridization (with an amplification ratio > 2.0 indicating positive) by each institute 3....

Data from 637 HER2+ patients with metastatic breast cancer enrolled in the multicenter Italian GIM14/BIOMETA study were retrieved….Overall, for first-line therapies, mPFS was 16.5 vs 19.5 months for patients treated in 2000-2013 vs 2014-2020 (HR: 0.78, 95% CI:0.65-0.94, P = 0.008). mPFS improved over time in all patients except for those with brain metastasis....Median first-line PFS improved since 2014, mainly due to the introduction of pertuzumab. The outcome of patients with liver metastases appears to have improved in recent years.

The aim of this retrospective study was to evaluate progesterone receptor (PR) status as a predictor of response to the addition of pertuzumab in HER2 + /N + breast cancer….HP-based therapy contributed to better DFS in the ER - and PR - cohorts (P = 0.035 and 0.015, respectively)....Compared with ER status, PR status might be a more valuable factor predicting the efficacy of adding pertuzumab into neoadjuvant therapy for HER2 + /N + BC. PR + patients benefit little from the addition of pertuzumab.

...clinical randomized controlled trials of treatment in combination with pertuzumab (experimental group) and without pertuzumab (control group) for HER2-positive breast cancer….The results from this study showed that, the patients in the experimental group showed prolonged progression-free survival [hazard ratio = 0.72, 95% confidence interval (CI) (0.65,0.80), P < .01] and overall survival [hazard ratio = 0.80, 95% CI (0.66,0.96), P = .02] than those in the control group....These results support that the treatment in combination with pertuzumab is superior to the treatment in combination without pertuzumab in the treatment of HER2-positive breast cancer...

Of 35 patients with HER2-positive mBC (median age, 49 years; range, 35-87 years), 14 received pertuzumab as a second-line therapy, 6 as a third-line therapy, and 15 as a fourth- or later-line therapy….The median overall survival was 74.2 months (95% confidence interval, 47.6-139.8 months)....In conclusion, the median overall survival of patients who underwent second- or later-line pertuzumab treatment was similar to that reported for patients who underwent first-line pertuzumab treatment, and the safety profile was acceptable.

We included data from all patients with a confirmed diagnosis of HER2+ MBC treated from 2014 to 2021... endpoints included adoption of pertuzumab-based regimen and T-DM1 in the palliative setting and their median Time to Treatment Discontinuation (TTD) in a real-world scenario....With a median follow-up of 2 years, median OS was 49 months (CI95% 44-59)….Overall, 62% received a pertuzumab-based regimen, mostly in the 1st line (76%), with median TTD of 9.9 months (CI95% 9-13)....In the largest Brazilian real-world study of patients with HER2+ MBC treated in the private health system, we found similar outcomes as those reported in North-American and European cohorts, both in terms of OS and TTD with standard-of-care therapies.

We collected data of all patients with stage II-III HER2-positive breast cancer....Overall, pCR rate was 65.0% in patients who received pertuzumab and 38.9% in patients who did not. In patients with single HER2-type tumors, pCR rate was significantly higher with pertuzumab (77.0% vs. 46.0%, multivariate adjusted odds ratio [aOR] 3.92, 95% confidence interval [CI] 2.60 - 5.98)....In addition, multivariate Cox regression analyses showed a significant OS benefit with pertuzumab in patients with single HER2-type tumors (adjusted hazard ratio [aHR] 0.33, 95% CI 0.16 - 0.67), but not in other subtypes (aHR 0.94, 95% CI 0.31 - 2.83).

We included 493 systemically treated patients consecutively diagnosed with HER2 + ABC in 2008-2017 from the SOutheast Netherlands Advanced BREast cancer (SONABRE) Registry….The median OS in 2008-2012 versus 2013-2017 was 28.3 versus 39.7 months in all patients (adjusted hazard ratio (adjHR) 0.85, 95%CI 0.66-1.08), 29.9 versus 36.3 months in patients with HR + /HER2 + disease (adjHR 0.97, 95%CI 0.72-1.32), and 22.7 versus 40.9 months in patients with HR-/HER2 + disease (adjHR 0.59, 95%CI 0.38-0.92).... The survival of patients with HER2 + ABC improved since the introduction of pertuzumab and T-DM1.