Heal her·Newborn | Southern Breast Cancer Diagnosis and Treatment Summit Forum was grandly held, big coffees gathered to explore hot issues in breast cancer treatment

■ Introduction On March 28, the Southern Breast Cancer Diagnosis and Treatment Summit Forum was successfully held.

This conference was hosted by Professor Huang Tao, Director of the Breast and Thyroid Surgery Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Professor Liu Qiang, Director of General Surgery at Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Professor Ouyang Taken, Director of Breast Medicine, Hunan Cancer Hospital, and Sun Yat-sen University Cancer Center Professor Wang Shusen, the chief expert of breast cancer single disease, served as the chairperson.
All the big coffee participants gathered together to have wonderful discussions and share opinions on the hot issues in the treatment of HER2-positive breast cancer at various stages.

(Experts’ names are arranged in pinyin of their surnames) On the occasion of this summit, Yimaitong had the honor to interview Professor Huang Tao and Professor Xiong Huihua, director of the Department of Comprehensive Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
"Treatment progress" to share.

The following will share this interview and some of the wonderful academic content of the conference.

Professor Huang Tao and Professor Xiong Huihua interview Professor Huang Tao: Application and progress of neoadjuvant/adjuvant therapy for HER2-positive breast cancer Yimaitong: Not all molecular subtypes of breast cancer are suitable for neoadjuvant therapy, and according to CSCO guidelines, HER2-positive Breast cancer patients can be treated with neoadjuvant drugs before surgery.

For such patients, what is the significance of neoadjuvant therapy? How do you usually choose a neoadjuvant treatment plan in the clinic? How effective are these programs? Professor Huang Tao: The clinical significance of neoadjuvant therapy for breast cancer is mainly reflected in three aspects: first, let the originally inoperable breast cancer become operable after downgrading; second, let the originally inoperable breast cancer or Patients who have difficulty in breast-conserving can become breast-sparing or get breast-conserving opportunities through neoadjuvant downgrading.
Third, neoadjuvant therapy is also a kind of drug sensitivity test in a sense, allowing us to treat patients and tumors.
, There is an intuitive evaluation of the sensitivity of the drug.

Previously, the neoadjuvant treatment of HER2-positive breast cancer mainly used trastuzumab combined with chemotherapy.

In recent years, clinical trials have proved that compared with trastuzumab single-target therapy, trapa dual-target therapy can greatly increase the pCR rate of HER2-positive breast cancer patients.

For example, in the NeoSphere study, the pCR rate of the dual-target therapy group of Trapa was 45.
8%, while the pCR rate of the single-target therapy group was only 29% (P=0.
014)1.

Our clinical trials in China have also proved that the pCR rate after dual-target treatment with Trapa is significantly higher than that of single-target2.

Therefore, for HER2-positive breast cancer, our first choice for neoadjuvant treatment is tripa dual-target combined chemotherapy.

Yimaitong: After neoadjuvant treatment, there are still 40%-60% of HER2-positive early breast cancer patients who have not achieved pathological complete remission (non-pCR).

Such patients have poor long-term survival.
Is there any follow-up plan that can improve the prognosis? Professor Huang Tao: Based on the current evidence-based medical evidence, for HER2-positive breast cancer, if pCR is not obtained during the neoadjuvant treatment stage, follow-up intensive treatment can further reduce its mortality.

Intensive treatment includes the use of T-DM1.

The KATHERINE study confirmed that compared with trastuzumab, the use of T-DM1 for intensive adjuvant therapy can reduce the risk of recurrence or death in non-PCR patients by 50%3.

Therefore, for patients with non-pCR breast cancer after HER2-positive neoadjuvant therapy, the guidelines recommend that T-DM1 is the first choice for intensive adjuvant therapy.

Yimaitong: In the adjuvant treatment stage, which patients are suitable for double-target therapy with Trapa? For patients with negative axillary lymph nodes who are at high risk of recurrence, do you think the double target of Trapa has application value? Professor Huang Tao: Patients with a high risk of death and recurrence are suitable groups for adjuvant therapy with Trapa dual target.

For patients with HER2-positive breast cancer with negative axillary lymph nodes but other high-risk factors, we need to consider a variety of factors when choosing a treatment plan, such as the status of the recipient, the size of the tumor, the presence or absence of vascular invasion, and the presence or absence of Cancer thrombus and so on.

For some of these patients, we will still choose the Trapa dual target.

Professor Xiong Huihua: The latest progress in the treatment of HER2-positive advanced breast cancer.
Yimaitong: What is the main treatment goal for patients with advanced breast cancer? Can you introduce the current first-line standard treatment strategy for HER2-positive advanced breast cancer? Professor Xiong Huihua: The goal of treatment for advanced breast cancer is to prolong the survival of patients and ensure their quality of life.

At present, for HER2-positive advanced breast cancer, domestic and foreign guidelines recommend the use of Trapa dual target + taxanes as the first-line standard treatment.

This recommendation is based on the CLEOPATRA trial, which is a multicenter, randomized, double-blind, placebo-controlled Phase III trial.

The subjects were assigned to the double target of tripa + taxanes group or trastuzumab + taxanes group.

In the end, the 8-year OS rate of dual-target therapy reached 37%.
Compared with the single-target therapy group, the median OS of the dual-target therapy group was extended from 40.
8 months to 57.
1 months4.

With a median OS of 57.
1 months, patients have the possibility of long-term survival.
Therefore, international guidelines regard the double target of Trapa as the standard treatment for first-line treatment of HER2-positive advanced breast cancer.

A bridging CLEOPATRA study designed by our research team-PUFFIN study 5, patients with HER2-positive advanced breast cancer were randomly assigned 1:1 to the Trapa dual target + docetaxel group or placebo + trastuzumab +Docetaxel group.

The results showed that the median PFS of the dual-target treatment group was longer than that of the single-target treatment group from 12.
4 months to 14.
5 months, which was the same as the HR value of the global CLEOPATRA study, which was both 0.
69.

It is suggested that the efficacy of dual-target therapy in Chinese advanced breast cancer patients is consistent with that of the global population, and it has established the first-line standard status of the dual-target regimen of Trapa in my country's HER2-positive advanced breast cancer.

Yimaitong: For patients who have used trastuzumab in the early stage, is there any application value for the double target of trapa? In your clinical work, how do you choose the trastuzumab re-use population? Professor Xiong Huihua: Trastuzumab has been used for more than 20 years, so in the adjuvant treatment stage, most patients may have used trastuzumab.

So if the patient relapses, does the double target of Trapa still have application value? The 2020 CSCO guidelines suggest that for this part of the population, tripa dual target combined with taxanes can still be used.

There are roughly three categories of people eligible for trastuzumab re-use: first, patients who have been effective trastuzumab in the previous neoadjuvant treatment phase; second, trastuzumab is used in the adjuvant phase, and the drug has been discontinued more than Patients who relapse after 12 months; third, patients who have used trastuzumab in the late stage and are effective, but have stopped the drug for some reason.

Recently, at the St.
Gallen conference in 2021, Professor Ma Fei’s team published the results of a meta-analysis, searched PubMed, ClinicalTrial, Embase and other databases, and included a total of 5 randomized controlled studies including CLEOPATRA.

The results showed that even for HER2-positive breast cancer patients who had previously used trastuzumab, Trapa dual target could still prolong PFS (HR=0.
80) and OS (HR=0.
76)6.

Therefore, for some patients who have previously used trastuzumab, the double target of trapa is still an effective treatment.

Yimaitong: For patients with HER2-positive advanced breast cancer who have progressed after first-line treatment, how should the second-line treatment be selected? Is there a plan that will benefit the patient's further survival? Professor Xiong Huihua: For patients with HER2-positive advanced breast cancer, on the road of anti-HER2, despite the difficulties encountered in the first-line treatment, the second-line continued anti-HER2 is still our goal.

For patients who have failed first-line anti-HER2 therapy, the choice of second-line therapy is different at home and abroad.

T-DM1 is recommended abroad, but the second-line indication of T-DM1 has not been approved in my country, so TKI drugs are used in combination with chemotherapy in China.

The PHOEBE study led by Professor Xu Binghe divided HER2-positive advanced breast cancer patients who had previously received trastuzumab combined with chemotherapy into two groups.
One group was treated with pyrrotinib + capecitabine, and the other group was treated with lapa.
Tinib + capecitabine treatment. The results showed that the median PFS of the pyrrotinib+capecitabine treatment group was 12.
5 months, while the median PFS of the lapatinib+capecitabine treatment group was only 6.
8 months7.

Based on the results of the EMILIA study, T-DM1 has been approved abroad as a standard for second-line anti-HER2 treatment.

The study divided HER2-positive advanced breast cancer patients who had previously been treated with taxanes combined with trastuzumab into two groups, one group was treated with T-DM1, and the other group was treated with lapatinib + capecitabine treatment.

The results showed that the median PFS of the T-DM1 group was 9.
6 months, and that of the lapatinib+capecitabine group was 6.
4 months (HR=0.
65, P＜0.
001).

The main difference between this study and the PHOEBE study is that, so far, the OS data of the PHOEBE study is not yet mature, but the median OS of the EMILIA study has been reached, of which the T-DM1 group is 30.
9 months, lapatinib + cappe The duration of the tabine group was 25.
1 months (HR=0.
68, P＜0.
001)8.

We look forward to the indication of T-DM1 for the second-line treatment of HER2-positive advanced breast cancer in my country as soon as possible, providing new treatment options for breast cancer patients in my country.

Sharing the wonderful content of the conference, heal her and see the day through the clouds-the way of neoadjuvant therapy for HER2-positive early breast cancer.
At the meeting, Professor Yao Feng from Wuhan University People’s Hospital discussed three key issues that need to be clarified in neoadjuvant therapy for HER2-positive early breast cancer.

Who should choose neoadjuvant therapy? Professor Yao Feng pointed out that neoadjuvant therapy should be oriented towards the purpose of healing, not just for surgery.

The indications of neoadjuvant therapy are no longer only based on clinical staging, but should be individually determined in combination with tumor molecular classification, clinical staging and patient wishes.

The 2020 CSCO guidelines point out that HER2-positive, triple-negative breast cancer (TNBC) is an indication for neoadjuvant therapy before surgery, and when only HER2-positive or triple-negative breast cancer is selected as the criteria for neoadjuvant therapy before breast surgery, the tumor should be >2 cm; The 2021 NCCN guidelines include cT1cN0 in the neoadjuvant therapy population, and the 2021 ASCO guidelines recommend that patients with high-risk HER2-positive or TNBC should undergo neoadjuvant system therapy.

Professor Yao Feng believes that for patients with HER2-positive early breast cancer, if there is a certain tumor burden or the need for "de-escalation" surgery, neoadjuvant therapy can be selected.

How to choose the initial plan of new adjuvant therapy for HER2-positive breast cancer? Professor Yao Feng believes that the “strongest” initial neoadjuvant regimen for HER2-positive breast cancer is the dual target of Trastuzumab (trastuzumab + Pertuzumab) combined with chemotherapy.

Neoadjuvant therapy should adopt a program that can obtain a higher pathological complete remission (pCR) rate, so that the originally sensitive patients can get more effective treatment, so that the originally insensitive patients become sensitive, and ultimately achieve the goal of cure.

MD Anderson retrospective analysis and PEONY study suggest that dual-target neoadjuvant therapy with Trapa can achieve a higher pCR rate than single-target therapy; and the TRAIN-2 study suggests that neoadjuvant therapy for HER2-positive breast cancer is based on dual-target Trapa With or without anthracyclines, there was no effect on pCR and event-free survival (EFS).

How does the curative effect of new adjuvant determine the follow-up treatment strategy? Professor Yao Feng interpreted the large-scale phase Ⅲ study KATHERINE.
The study showed that patients with HER2-positive early breast cancer who did not achieve complete pathological remission (non-pCR) after neoadjuvant treatment, enmetrastuzumab (T-DM1) can make Its survival benefit.

He pointed out that the KATHERINE study suggests that non-pCR patients have drug-resistant strains and require adjuvant intensive treatment, and the success of adjuvant intensive treatment comes from increasing treatment or reversing drug resistance.

According to the latest NCCN guidelines, for HER2-positive patients, regardless of their HR status, if neoadjuvant treatment of residual lesions, T-DM1 alone is recommended for 14 cycles.

Professor Yao Feng suggested that for patients with effective neoadjuvant therapy, a full course of treatment (at least 6 courses) should be completed: if the patient reaches pCR, the adjuvant tripa dual target for 1 year; for non-pCR patients, based on evidence-based medical evidence, Can assist T-DM1 strengthening.

For patients with poor curative effect, it is necessary to consider surgery as soon as possible, postoperative auxiliary EC program (doxorubicin + cyclophosphamide) and so on.

Healing her • Chasing after victory-Adjuvant treatment of node-negative and HER2-positive breast cancer Professor Chen Qianjun from Guangdong Provincial Hospital of Traditional Chinese Medicine discussed at the meeting whether it is necessary to use Trapa dual target for adjuvant treatment of lymph node-negative and HER2-positive breast cancer.

Professor Chen Qianjun first pointed out that the 6-year iDFS subgroup analysis results of the APHINITY study showed that compared with the control group, the double-target adjuvant treatment with Trapa increased the 6-year DFS rate of patients with positive lymph nodes by 4.
5%, while the 6-year DFS rate of patients with negative lymph nodes increased by 4.
5%.
The absolute increase in DFS rate is almost 0%.

In response to this result, he believes that the possible reason is that the inclusion of too many lower-risk groups "dilutes" the benefits of lymph node-negative patients.

Professor Chen Qianjun believes that not all lymph node-negative and HER2-positive breast cancers do not require the double target of Trapa.

Subsequently, in response to this point of view, Professor Chen Qianjun discussed the following three issues from the perspective of treatment benefit and treatment damage.

Does negative lymph node affect anti-HER2 "treatment damage"? Professor Chen Qianjun said that the analysis of trastuzumab in the treatment of elderly breast cancer patients (age> 66 years old) showed that drug-related cardiotoxicity was related to advanced age (age> 80 years old), cardiovascular disease, and weekly trastuzumab therapy , But it has nothing to do with lymph node status; APHINITY study shows that the double target of trama does not significantly increase the heart safety problem.

Therefore, Professor Chen Qianjun believes that the negative lymph node does not affect the drug toxicity of anti-HER2 therapy.

Does negative lymph node affect the sensitivity of dual-target therapy with Trapa? Professor Chen Qianjun pointed out that the sensitivity of Trapa dual-target therapy depends on molecular biological behavior and has little to do with lymph node status.

After trastuzumab single-target therapy, what is the risk of recurrence in patients with negative lymph nodes? Professor Chen Qianjun pointed out that the 10-year data of the B31/N9831 study showed that after 1-year trastuzumab treatment in patients with lymph node-negative and HER2-positive breast cancer, the 10-year cumulative risk of DFS exceeded 10% (HR+: 10.
94%; HR-: 24.
94%), which means that these patients still have a higher risk of recurrence with trastuzumab alone, and may require dual-target therapy with trapa.

Professor Chen Qianjun concluded that for patients with node-negative and HER2-positive breast cancer, if there is a higher risk of recurrence, it is still necessary to use dual-target adjuvant therapy with Trapa.

How to use traditional prognostic indicators to identify high-risk groups is worthy of further exploration.

Heal her • Persevere——Professor Xiong Huihua shared her views on the theme of "Treatment progress and decision-making layout of HER2-positive advanced breast cancer" at the meeting.

First-line treatment options for HER2-positive advanced breast cancer Professor Xiong Huihua pointed out that in the treatment of advanced breast cancer, OS improvement is an important efficacy consideration standard recommended by authoritative guidelines; based on OS benefits, NCCN guidelines and ABC4 guidelines recommend Pertuzumab+ Trastuzumab + taxanes is the first-line regimen for HER-positive advanced breast cancer.

CLEOPATRA is a key study that verifies that the double target of trama has become the new standard program for the late stage.
The 8-year follow-up results showed that the median OS of the trastuzumab single target group was 40.
8 months, while the median OS of the double target group of trastuzumab reached 57.
1 months, and the cardiotoxicity did not increase significantly.

The PUFFIN study further verified the effectiveness of the double target of trama in the Chinese population.

Based on the studies of CLEOPATRA and PUFFIN, Trapa dual target has become the first-line treatment of choice for HER2-positive advanced breast cancer both internationally and domestically.

In addition, the CLEOPATRA subgroup analysis showed that for patients who were previously treated early with trastuzumab (disease-free interval> 12 months after treatment), the trapa dual target group reduced the risk of disease progression by 38% compared with single target therapy, and death The risk is reduced by 32%.

A meta-analysis at the 2021 St.
Gallen meeting confirmed that for patients who have previously received trastuzumab therapy, advanced first-line trapa dual-target therapy for PFS and OS has significant benefits.

Second-line treatment options for HER2-positive advanced breast cancer Professor Xiong Huihua stated that since T-DM1 has not yet been approved for the second-line treatment of advanced HER2-positive breast cancer in my country, there are differences in the choice of second-line therapy between China and the West.

According to the EMILIA study, T-DM1 significantly prolonged PFS and OS in HER2-positive second-line patients compared with lapatinib + capecitabine (LX), and cross-treatment patients who switched from LX therapy to T-DM1 therapy can also switch from T-DM1 to T-DM1.
OS was improved in the subgroups, and the PFS and OS of the subgroups had the same benefits; in addition, the second-line treatment of T-DM1 was also effective for patients with brain metastases.
The EMILIA study showed that T-DM1 significantly prolonged the OS of patients with brain metastases and reduced the OS of patients with brain metastases compared with LX.
The risk of death is 62%.

The PERNETTA study and the TDM1RM study indicate that patients with HER2-positive advanced breast cancer who receive either the first-line Trapa dual-target combined chemotherapy or trastuzumab combined chemotherapy can benefit from T-DM1 treatment after progression.

Professor Xiong Huihua believes that animal models show that the tumor shrinks again after the addition of pertuzumab to trastuzumab, confirming that heterodimers are one of the resistance mechanisms of trastuzumab; for the first-line For the treatment of patients who have not used Pertuzumab, the dual-target combination chemotherapy with Trapa can be used as a second-line option for HER2-positive advanced breast cancer.

References: 1.
GIANNI L, et al.
The Lancet Oncology, 2016, 17 (6): 791-800.
2.
SHAO Z, et al.
JAMA oncology, 2019, 13(1):25-32.
3.
von Minckwitz G, et al.
N Engl J Med.
2019 Feb 14;380(7):617-628.
4.
Garcia JM, et al.
Annals of Oncology (2020) 31 (suppl_4): S348-S395.
5.
Binghe Xu, et al.
2019 ASCO.
Abstract 1026.
6.
Chen S, et al.
Poster presentation at St.
Gallen International Breast Cancer Conference; March 17-21, 2021.
Abstract P059.
7.
Xu BH, et al.
2020 ASCO, abstract 1003.
8.
Baselga J, et al.
N Engl J Med.
2012 Jan 12;366(2):109-19.