Evaluation of clinical and pathological responses of HER-2 positive locally advanced breast cancer patients after neoadjuvant therapy and surgery
Öz
Purpose: This study aimed to compare the effectiveness and toxicity of neoadjuvant dual Human epidermal growth factor receptor-2 (HER-2) blockade combined with chemotherapy in advanced breast cancer.
Materials and Methods: Patients with HER2-positive breast cancer who received trastuzumab (T)+ pertuzumab (P) with weekly neoadjuvant paclitaxel or docetaxel were included in the study. Patients’ age, clinical stage, histological reports, ki-67 index, toxicity profiles, and the state of the pathological and radiological response following neoadjuvant therapy were evaluated.
Results: All 40 patients were women (mean age 50.9) and the overall rate of pathological complete responses was 62.5% (25/40). The rates of non-responsive patients and grade 2 neuropathy were statistically significantly higher in the group receiving P+T+Weekly Paclitaxel. When SUV values were analyzed based on hormone positivity, it was found that they decreased dramatically in both groups and were statistically significant. The logistic regression analysis developed to predict the precise response status to therapy was found to be significant.
Conclusion: When comparing the agents used in dual HER-2 targeted therapies, patient response rates and toxicity profiles may differ. Ductal carcinoma in situ (DCIS) and molecular subtype were found to be significant variables in the developed logistic regression model.
Anahtar Kelimeler
Kaynakça
- Hanna WM, Rüschoff J, Bilous M, Coudry RA, Dowsett M, Osamura RY et al. HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity. Mod Pathol. 2014;27:4-18.
- Yang YL, Fan Y, Lang RG, Gu F, Fu L. Association of HER2 genetic heterogeneity with clinicopathological characteristics in breast cancer. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010;27:540-5.
- Schroeder RL, Stevens CL, Sridhar J. Small molecule tyrosine kinase inhibitors of ErbB2/HER2/Neu in the treatment of aggressive breast cancer. Molecules. 2014;19:15196-212.
- Osborne CK, Schiff R, Rimawi M. DE-escalating treatment for her2-positive early breast cancer. Trans Am Clin Climatol Assoc. 2020;131:119-26.
- Yu L, Fu F, Li J, Huang M, Zeng B, Lin Y et al. Dual HER2 blockade versus a single agent in trastuzumab-containing regimens for HER2-positive early breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Oncol. 2020;2020:5169278.
- Ashrafizadeh M, Mirzaei S, Hashemi F, Zarrabi A, Zabolian A, Saleki H et al. New insight towards development of paclitaxel and docetaxel resistance in cancer cells: EMT as a novel molecular mechanism and therapeutic possibilities. Biomed Pharmacother. 2021;141:111824.
- Zhang X, Chen J, Weng Z, Li Q, Zhao L, Yu N et al. A new anti-HER2 antibody that enhances the anti-tumor efficacy of trastuzumab and pertuzumab with a distinct mechanism of action. Mol Immunol. 2020;119:48-58.
- von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377:122-31.
- Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004;5:317-28.
- Lv M, Guo H, Wang C, Tian P, Ma Y, Chen X et al. Neoadjuvant docetaxel with or without carboplatin plus dual HER2 blockade for HER2-positive breast cancer: a retrospective multi-center Chinese study. Gland Surg. 2020;9:2079-90.
- Pernas S, Tolaney SM. HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance. Ther Adv Med Oncol. 2019;11:1758835919833519.
- Celik A, Berg T, Nielsen LB, Jensen MB, Ejlertsen B, Knoop A et al. First-line treatment of HER2-Positive metastatic breast cancer with dual blockade including biosimilar trastuzumab (sb3): population-based real-world data from the DBCG. Breast Cancer (Auckl). 2022;16:11782234221086992.
- Advani P, Cornell L, Chumsri S, Moreno-Aspitia A. Dual HER2 blockade in the neoadjuvant and adjuvant treatment of HER2-positive breast cancer. Breast Cancer (Dove Med Press). 2015;7:321-35.
- Guarneri V, Frassoldati A, Bottini A, Cagossi K, Bisagni G, Sarti S et al. Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol. 2012;30:1989-95
- Zhang H, Katerji H, Turner BM, Audeh W, Hicks DG. HER2-low breast cancers: incidence, HER2 staining patterns, clinicopathologic features, MammaPrint and BluePrint genomic profiles. Mod Pathol. 2022;35:1075-82.
- Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724-34.
- Loibl S, Gianni L. HER2-positive breast cancer. Lancet. 2017;389:2415-29.
- Wang C, Chen J, Xu X, Hu X, Kong D, Liang G et al. Dual HER2 blockade in neoadjuvant treatment of HER2+ breast cancer: a meta-analysis and review. Technol Cancer Res Treat. 2020;19:1533033820960721
HER-2 pozitif lokal ileri meme kanseri hastalarının neoadjuvan tedavi ve cerrahi sonrası klinik ve patolojik yanıtlarının değerlendirilmesi
Öz
Amaç: Bu çalışmanın amacı, ilerlemiş meme kanserinde neoadjuvan dual insan epidermal büyüme faktörü reseptörü 2 (HER2) blokajında kullanılan kemoterapotiklerin etkinliğini ve toksisitesini karşılaştırmaktı.
Gereç ve Yöntem: Haftalık neoadjuvan paklitaksel veya dosetaksel ile trastuzumab (T)+ pertuzumab (P) alan HER2 pozitif meme kanserli hastalar çalışmaya dahil edildi. Hastaların yaşı, klinik evresi, histolojik raporları, ki-67 indeksi, toksisite profilleri ve neoadjuvan tedavi sonrası patolojik ve radyolojik yanıt durumu değerlendirildi.
Bulgular: Çalışmaya dahil edilen 40 hastanın tümü kadındı (ortalama yaş 50.9) ve genel patolojik tam yanıt oranı %62.5 idi (25/40). Haftalık P+T+Paklitaksel alan grupta tedaviye yanıtsız hasta ve grade 2 nöropati oranları istatistiksel olarak anlamlı derecede yüksekti. SUV değerleri hormon pozitifliğine göre analiz edildiğinde, her iki grupta da önemli ölçüde azaldığı ve istatistiksel olarak anlamlı olduğu bulundu. Tedaviye kesin yanıt durumunu tahmin etmek için geliştirilen lojistik regresyon analizi anlamlı bulunmuştur.
Sonuç: Dual HER-2 hedefli tedavilerde kullanılan ajanlar karşılaştırıldığında hasta yanıt oranları ve toksisite profilleri farklı olabilmektedir. Geliştirilen lojistik regresyon modelinde duktal karsinom in situ (DCIS) ve moleküler alt tipin anlamlı değişkenler olduğu bulunmuştur.
Anahtar Kelimeler
Kaynakça
- Hanna WM, Rüschoff J, Bilous M, Coudry RA, Dowsett M, Osamura RY et al. HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity. Mod Pathol. 2014;27:4-18.
- Yang YL, Fan Y, Lang RG, Gu F, Fu L. Association of HER2 genetic heterogeneity with clinicopathological characteristics in breast cancer. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010;27:540-5.
- Schroeder RL, Stevens CL, Sridhar J. Small molecule tyrosine kinase inhibitors of ErbB2/HER2/Neu in the treatment of aggressive breast cancer. Molecules. 2014;19:15196-212.
- Osborne CK, Schiff R, Rimawi M. DE-escalating treatment for her2-positive early breast cancer. Trans Am Clin Climatol Assoc. 2020;131:119-26.
- Yu L, Fu F, Li J, Huang M, Zeng B, Lin Y et al. Dual HER2 blockade versus a single agent in trastuzumab-containing regimens for HER2-positive early breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Oncol. 2020;2020:5169278.
- Ashrafizadeh M, Mirzaei S, Hashemi F, Zarrabi A, Zabolian A, Saleki H et al. New insight towards development of paclitaxel and docetaxel resistance in cancer cells: EMT as a novel molecular mechanism and therapeutic possibilities. Biomed Pharmacother. 2021;141:111824.
- Zhang X, Chen J, Weng Z, Li Q, Zhao L, Yu N et al. A new anti-HER2 antibody that enhances the anti-tumor efficacy of trastuzumab and pertuzumab with a distinct mechanism of action. Mol Immunol. 2020;119:48-58.
- von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377:122-31.
- Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004;5:317-28.
- Lv M, Guo H, Wang C, Tian P, Ma Y, Chen X et al. Neoadjuvant docetaxel with or without carboplatin plus dual HER2 blockade for HER2-positive breast cancer: a retrospective multi-center Chinese study. Gland Surg. 2020;9:2079-90.
- Pernas S, Tolaney SM. HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance. Ther Adv Med Oncol. 2019;11:1758835919833519.
- Celik A, Berg T, Nielsen LB, Jensen MB, Ejlertsen B, Knoop A et al. First-line treatment of HER2-Positive metastatic breast cancer with dual blockade including biosimilar trastuzumab (sb3): population-based real-world data from the DBCG. Breast Cancer (Auckl). 2022;16:11782234221086992.
- Advani P, Cornell L, Chumsri S, Moreno-Aspitia A. Dual HER2 blockade in the neoadjuvant and adjuvant treatment of HER2-positive breast cancer. Breast Cancer (Dove Med Press). 2015;7:321-35.
- Guarneri V, Frassoldati A, Bottini A, Cagossi K, Bisagni G, Sarti S et al. Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol. 2012;30:1989-95
- Zhang H, Katerji H, Turner BM, Audeh W, Hicks DG. HER2-low breast cancers: incidence, HER2 staining patterns, clinicopathologic features, MammaPrint and BluePrint genomic profiles. Mod Pathol. 2022;35:1075-82.
- Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724-34.
- Loibl S, Gianni L. HER2-positive breast cancer. Lancet. 2017;389:2415-29.
- Wang C, Chen J, Xu X, Hu X, Kong D, Liang G et al. Dual HER2 blockade in neoadjuvant treatment of HER2+ breast cancer: a meta-analysis and review. Technol Cancer Res Treat. 2020;19:1533033820960721
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Cerrahi Onkoloji, Klinik Onkoloji |
| Bölüm | Araştırma |
| Yazarlar | |
| Erken Görünüm Tarihi | 26 Eylül 2023 |
| Yayımlanma Tarihi | 30 Eylül 2023 |
| Kabul Tarihi | 19 Eylül 2023 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 48 Sayı: 3 |
