I.V. Kolyadina
Russian Medical Academy of Continuing Professional Education, Moscow, Russia
L.É. Zavalishina
FGBU "Moskovskiĭ nauchno-issledovatel'skiĭ onkologicheskiĭ institut im. P.A. Gertsena" Minzdravsotsrazvitiia Rossii
I.P. Ganshina
N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
Yu.Yu. Andreeva
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
G.A. Frank
Moskovskiĭ nauchno-issledovatel'skiĭ onkologicheskiĭ institut im. P.A. Gertsena Rosmedtekhnologiĭ, Moskva
O.O. Gordeeva
N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
L.G. Zhukova
FGBU "Rossiĭskiĭ onkologicheskiĭ nauchnyĭ tsentr im. N.N. Blokhina", Moskva
A.A. Meshcheryakov
Educational and Research Medical Center of Presidential Administration of the Russian Federation, Moscow
Савелов Н. А.
E.A. Tuzova
Moscow City Oncology Hospital #62, Moscow Healthcare Department, Moscow, Russia
D.A. Morozov
Saratovskiĭ gosudarstvennyĭ meditsinskiĭ universitet im. V.I. Razumovskogo Roszdrava, NII fundamental'noĭ i klinicheskoĭ uronefrologii Saratovskogo GMU
I.V. Poddubnaia
Kafedra onkologii RMAPO, Moskva
Role of clustered amplification as a marker for a special sensitivity to neoadjuvant anti-HER2 therapy with trastuzumab in patients with stage II—III breast cancer
Journal: Russian Journal of Archive of Pathology. 2019;81(6): 56‑62
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To cite this article:
Kolyadina IV, Zavalishina LÉ, Ganshina IP, Andreeva YuYu, Frank GA, Gordeeva OO, Zhukova LG, Meshcheryakov AA, Tuzova EA, Morozov DA, Poddubnaia IV. Role of clustered amplification as a marker for a special sensitivity to neoadjuvant anti-HER2 therapy with trastuzumab in patients with stage II—III breast cancer. Russian Journal of Archive of Pathology.
2019;81(6):56‑62. (In Russ., In Engl.)
https://doi.org/10.17116/patol20198106156
Objective — to evaluate the influence of clinical and morphological factors and HER2 copy numbers on pathologic complete response (pCR) rates in patients with HER2-positive stage II—III breast cancer (BC). Subject and methods. Treatment results were studied in 73 patients with HER2-positive Stage II—III BC, who received treatment at the N.N. Blokhin National Medical Research Center of Oncology in 2015 to 2018. Treatment included neoadjuvant chemotherapy (NACT) with HER2-blockade and radical surgery followed by the evaluation of a pathologic response in the primary tumor and regional lymph nodes. The patients` age varied from 29 to 71; its median was 51.5; 45.2% of patients had primary operable stages (T1-3N0-1) and 54.8% had locally advanced tumors. All the patients had grade 2—3 anaplasia; luminal HER2-positive BC was diagnosed in 41.4% of patients; hormone-negative tumors were seen in 58.9%; 91.5% of patients had Ki-67 ≥20% in 75.3% of patients, preoperative systemic therapy included anthracycline-containing regimens (4AC + 4 x paclitaxel 175 mg/m2/12 × weekly administrations of paclitaxel 80 mg/m2; trastuzumab therapy was simultaneously performed with the administration of taxanes in the standard regimen) and anthracycline-free regimen TCH ± Pertuzumab regimen in 24.7% of cases. After NACT patients underwent surgery (radical mastectomy in 78.1%, breast-sparing treatment in 21.9%) with the assessment of morphological findings. Biopsy specimens obtained before the treatment was restudied; HER2 amplification was detected using a Dako HER2 IQFISH pharmDx kit according to its instruction and the 2018 ASCO/CAP guidelines. In 87.1% of cases, the HER2-positive status corresponded to the first category of the 2018 ASCO/CAP criteria for HER2-positive BC; clustered HER2 amplification was found in 30.1% of cases. The authors analyzed the frequency of bpCR and tpCR attainment by various clinical and morphological factors, as well as the impact of a HER2 amplification level on pCR rates. Results. A breast pCR (bpCR) was achieved in 57.4% patients; bpCR and lymph node CR (lnCR) were noted in 48.9% patients. The rates of bpCR significantly depended on female age, chemotherapy regimen, addition of Pertuzumab, and HER2 copy number. That of bpCR in women less than 35 years of age, in those aged 36—50 years, and in those aged older than 50 years was 22.2, 57.7 and 71.9%, respectively (p=0.026). The maximum bpCR rate observed with the TCH±P regimen was 80.0%, that with anthracycline-containing regimes was 52.8% (p=0.045), and the addition of Pertuzumab increased complete response rates up to 88.9% (that with Trastuzumab was 54.2% (p=0.049). The relationship of bpCR rates to the detection of cluster amplification turned out to be highly significant (81% in its detection and 48.9% in its absence (p=0.013). In addition, clustered HER2 amplification was the only significant predictive factor for complete regression in the primary tumor and lymph nodes: in its presence, the tpCR rate reached 68.8% versus 38.7%. Conclusion. Clustered amplification of the HER2 gene is the most significant factor of sensitivity to anti-HER2 therapy for Stage II—III BC, and is associated with the maximum rate of both bpCR and total pCR. Further study of this factor may assist in optimizing the treatment algorithm for HER2 + BC.
Keywords:
Authors:
I.V. Kolyadina
Russian Medical Academy of Continuing Professional Education, Moscow, Russia
L.É. Zavalishina
FGBU "Moskovskiĭ nauchno-issledovatel'skiĭ onkologicheskiĭ institut im. P.A. Gertsena" Minzdravsotsrazvitiia Rossii
I.P. Ganshina
N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
Yu.Yu. Andreeva
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
G.A. Frank
Moskovskiĭ nauchno-issledovatel'skiĭ onkologicheskiĭ institut im. P.A. Gertsena Rosmedtekhnologiĭ, Moskva
O.O. Gordeeva
N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
L.G. Zhukova
FGBU "Rossiĭskiĭ onkologicheskiĭ nauchnyĭ tsentr im. N.N. Blokhina", Moskva
A.A. Meshcheryakov
Educational and Research Medical Center of Presidential Administration of the Russian Federation, Moscow
Савелов Н. А.
E.A. Tuzova
Moscow City Oncology Hospital #62, Moscow Healthcare Department, Moscow, Russia
D.A. Morozov
Saratovskiĭ gosudarstvennyĭ meditsinskiĭ universitet im. V.I. Razumovskogo Roszdrava, NII fundamental'noĭ i klinicheskoĭ uronefrologii Saratovskogo GMU
I.V. Poddubnaia
Kafedra onkologii RMAPO, Moskva
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