2021 CSCO Breast Cancer Guidelines: Interpretation of the updated key points of HER2+ neoadjuvant treatment for early breast cancer | 2021 CSCO BC

*Only for medical professionals to read and reference HER2+ Early Breast Cancer Neoadjuvant Therapy Update Detailed Interpretation~The 2021 National Breast Cancer Conference and Chinese Society of Clinical Oncology (CSCO) Breast Cancer Annual Meeting will be held in Beijing on April 9-10.

At the meeting, Professor Wang Kun from Guangdong Provincial People's Hospital interpreted the "2021 CSCO Breast Cancer Guidelines HER2+ New Adjuvant Treatment Update Points for Early Breast Cancer".

Professor Wang introduced that the 2021 version of the CSCO Breast Cancer Guidelines for preoperative neoadjuvant therapy updates for HER2+ early breast cancer focuses on three aspects: neoadjuvant therapy indications, neoadjuvant therapy level I recommendation, and adjuvant therapy options after neoadjuvant therapy.

Indications for neoadjuvant therapy: Combining clinical staging and molecular typing as the basis for the CSCO guidelines of the 2021 edition still emphasizes that the indications for neoadjuvant therapy before surgery should be determined individually based on tumor molecular classification, clinical staging and patient wishes.

This concept was also first proposed by CSCO in China in 2018, that is, for patients with HER2+ breast cancer, if the tumor is ≥2 cm (T>2) or has lymph node metastasis (N≥1), neoadjuvant therapy is recommended.

Figure 1 The 2021 version of the CSCO guidelines on the indications of preoperative neoadjuvant therapy.
For the National Comprehensive Cancer Network (NCCN) guidelines, the 2018 version still only determines the indications for neoadjuvant therapy based on clinical staging; the 2020 and 2021 versions point out that for HER2+ For triple-negative breast cancer, if T≥2 or N≥1, neoadjuvant therapy is recommended.

It can be seen that the concept of combining molecular classification and clinical staging proposed by the CSCO guidelines is 2 years earlier than the NCCN guidelines.

Figure 2 NCCN Guidelines Recommendations of the 2018 and 2020 Editions However, the 2021 American Society of Clinical Oncology (ASCO) guidelines point out that neoadjuvant therapy should not be routinely given to patients with T1a and T1b.

This means that patients with T1c can be treated with neoadjuvant therapy.

In view of the fact that the concept of “neoadjuvant treatment for T1c patients” has not been verified by clinical research and practice, the CSCO breast cancer guidelines still adopt the most advanced and feasible selection criteria currently considered, that is, for HER2+, T≥2 or N≥1 The patient was given neoadjuvant therapy.

Figure 3 The 2021 version of the CSCO guidelines recommends neoadjuvant treatment level I recommendation: TCbHP and THP The 2021 version of the CSCO breast cancer guidelines point out that for HER2+ breast cancer neoadjuvant treatment strategies, TCbHP and THP are level I recommendations, while the commonly used AC-THP is II Level recommendation; for the adjuvant treatment of HER2+ breast cancer, level I recommends AC-THP and TCbHP (T: taxanes; A: anthracyclines; C: cyclophosphamide; Cb: carboplatin: H: trastuzumab; P: Pertuzumab).

Figure 4 2021 CSCO breast cancer guidelines recommendation For NCCN guidelines, the 2020 version recommends 8 options for the neoadjuvant/adjuvant treatment options for HER2+ breast cancer; however, the 2021 version emphasizes deanthracyclization and recommends TCHP as the first choice, and AC as the second choice -THP, but it is still a unified recommendation for neoadjuvant and adjuvant therapy.

So, when adjuvant therapy, instead of AC-THP, is TCHP the first choice? This is questionable.

Figure 5 2020 and 2021 NCCN Guidelines Recommendations However, at the 2021 St.
Gallen meeting, 84.
62% of experts believe that anthracyclines do not need to be administered to patients with HER2+ without lymph node metastasis; for patients with lymph node metastasis, 61.
82% Of experts believe that anthracyclines should be given. Then, for the NCCN guidelines and the St.
Gallen consensus, there must be two points of contention: First, should neoadjuvant treatment use adjuvant treatment options? Second, due to the BCIRG 006 research complex, the survival of auxiliary AC-TH = survival of neo-assisted? That is to say, must the good curative effect of the anthracycline-containing program in adjuvant therapy be put into the field of neoadjuvant? Regarding controversy 1, Professor Wang explained: There are actually many inconsistencies between neoadjuvant therapy and adjuvant therapy.
The background of neoadjuvant therapy is the existence of tumors.
The short-term goal is to shrink the tumor or even achieve pathological complete remission (pCR).
The long-term goal It is to improve survival [event-free survival (EFS)]; the background of adjuvant treatment is that the tumor has been removed, and the goal is to improve survival [disease-free survival (DFS) or overall survival (OS)].

Therefore, for neoadjuvant therapy, adjuvant therapy can be used, but it is not optimal.

Regarding the second argument, the 10-year follow-up results (survival curve) of the BCIRG 006 study let everyone keep in mind that the survival curve of AC-TH has always been above TCH; although TCH is not inferior to AC-TH at 10 years, But the former is not better than the latter.

Figure 6 The 10-year follow-up results of the BCIRG 006 study.
However, for the recommendation of the neoadjuvant program, in addition to the routine consideration of the DFS of the adjuvant program, it is also necessary to consider whether the neoadjuvant phase is disease progression (PD) and whether to obtain a better pCR.
The combination of those is the survival index EFS considered by the neoadjuvant.

Therefore, the comparison between the anthracycline-containing regimen and the anthracycline-free regimen is to compare which regimen can achieve better local control rate in the first 3 to 4 cycles of treatment.

Figure 7 The definition of event-free survival The Phase II TRYPHAENA study tells us that comparing FEC (fluorouracil + epirubicin + cyclophosphamide) sequential yew + dual target (pertuzumab + trastuzumab) and dual In the target + purple shirt program, the results showed that the pCR of the TCHP program without anthracycline was 66%, which was higher than that of the TCHP program with anthracycline; there was no HR positive or negative, and the results were consistent.

Figure 8 TRYPHAENA study design and pCR results The TRAIN-2 study showed that the pCR of the 6-cycle TCHP+anthracycline+dual target program was not superior to the TCHP program without anthracycline, and the EFS results of the two groups were also similar.

Figure 9 TRAIN-2 study design and pCR results.
In addition, clinical studies in my country have shown that the addition of anthracyclines and dual-target drugs in the neoadjuvant treatment phase will increase the risk of febrile neutropenia, and about 1/3 of patients have it The left ventricular function decreased.

"Based on the above evidence-based medical evidence and the consensus of Chinese experts, the 2021 version of the CSCO breast cancer guidelines still recommends TCbHP and THP at level I, and AC-THP at level II.

" Professor Wang emphasized.

The choice of adjuvant therapy after neoadjuvant therapy: The stratified model is for single-target or dual-target therapy in the neoadjuvant phase.
The 2021 version of the CSCO guidelines provides a hierarchical analysis of subsequent adjuvant therapy strategies.

Since dual targets have not been popularized some time ago, some patients have used single-target therapy, and the CSCO guideline provides HP and T-DM1 options for cases where pCR is not obtained after single-target therapy.
This is very consistent with the current domestic treatment practice.

Figure 10: HER2+ breast cancer adjuvant treatment strategy after neoadjuvant treatment The 2021 version of the CSCO guidelines pointed out that for patients who did not achieve pCR after dual-target therapy, follow-up treatment was decided according to the Miller&Payen classification: when the tumor regression is particularly obvious, that is, the Miller&Payen classification reaches 3~ At level 4, dual-target therapy can be continued; for the tumor shrinkage is not obvious, that is, in the case of Miller&Payen classification of level 1 or 2, the expert group agreed to switch to a more suitable T-DM1 for treatment.

Figure 11 The updated content of the CSCO breast cancer guidelines in the 2021 edition.
However, the 2021 edition of the NCCN guidelines emphasizes that for HER2+ patients with residual tumors, T-DM1 is the first choice.
When T-DM1 is intolerable, dual-target therapy is given.

It can be seen that in addition to the evidence-based medicine evidence, the CSCO guidelines also consider the availability of medicines.

At present, T-DM1 does not have medical insurance coverage, and the price is very expensive.
Under such circumstances, the recommendations given by the CSCO guidelines are very down-to-earth and very Suitable for Chinese practice.

" Professor Wang said.

Summary: Regarding the updated points of preoperative neoadjuvant/adjuvant therapy for HER2+ early breast cancer, Professor Wang summarized as follows: In terms of neoadjuvant therapy indications, for HER2-positive patients, T≥2 or N≥1 is currently required; for neoadjuvant treatment options TCbHP and THP are recommended for level I; AC-THP and TCbHP are recommended for level I; for adjuvant therapy after neoadjuvant therapy, a hierarchical treatment model is recommended, that is, decisions are made based on neoadjuvant therapy and postoperative pathological evaluation .

For the future, Professor Wang is full of longing and confidence: "I hope that the CSCO breast cancer guidelines can do better and let our Chinese standards become the world standards!" Expert profile Professor Wang Kun, a famous doctor of the country, chief physician, doctoral tutor, people of Guangdong Province Director of the Second Department of Breast, CSCO Director, CSCO Breast Cancer Special Committee Standing Committee Member, Chinese Anti-Cancer Association Breast Cancer Specialty Committee (CACA-CBCS) Member, Guangdong Provincial Medical Association Breast Disease Branch Deputy Chairman, Guangdong Provincial Medical Association Breast Disease Branch Youth Committee chairman Wen starters: the medical profession tumor channel author: Cindy article review: Professor Wang Kun editor: Sharon original copyright notice for reprint this article, please contact your authorized - End -