ESMO 2022 takes stock of the highlights of early breast cancer

The 2022 European Society for Internal Oncology (ESMO) Annual Meeting was held

DATA Research

AI sequential extension to more than 5 years is not recommended for all postmenopausal HR-positive breast cancer patients

For postmenopausal hormone receptor (HR)-positive early-stage breast cancer, 5-year endocrine therapy has been the standard of

The DATA study was designed to assess the benefit of patients with HR-positive early-stage breast cancer who continued to receive 3- or 6-year anastrozole therapy after 2 to 3 years of adjuvant therapy with tamoxifen

The results showed that the DFS rates after 10-year correction were 69.

Further stratification analysis showed a significant benefit from 10-year correction of DFS in the prolonged endocrine therapy group compared with a single positive population, and the absolute benefit was significantly increased

The DATA findings suggest that AI sequential prolongation to more than

brief summary

The results of many clinical trials of extended therapy after 5 years of AI-assisted endocrine therapy are inconsistent, and GIM4 studies have shown that after 2 to 3 years of amoxifen treatment, adjuvant therapy regimens that extend the use time of letrozole can bring greater benefits to postmenopausal HR+ breast cancer patients; In the NSABP B42 study, the AI treatment group with extended 5 years increased overall DFS by 3.
4% compared with the placebo group, which did not achieve a statistical difference but showed a trend of clinical benefit; In the DATA study, after 2-3 years of his moxifen, the absolute benefit of the DFS rate after 10-year correction was 3.
1% compared with 3-year AI, although it also did not reach a statistically significant difference, but the absolute benefit increased
significantly in high-risk groups such as lymph node positive, ER and PR positive, tumor > 2cm.

In response to these arguments, EBCTCG conducted a meta-analysis that included 12 previous major randomized studies that showed that in patients receiving 5 years of initial or sequential AI, continued prolongation of AI for 3-5 years reduces the risk of
recurrence and death.

Further analysis found that high-risk populations inducted by various methods such as relative inadequate previous treatment, positive lymph nodes, positive hormone receptors, or genetic testing had significant
benefits.

In addition, the clinical treatment score (CTS5) after 5 years and multigenic testing tools are recommended to guide prolonged endocrine therapy ^decisions1
.

GlM2 study

Dose-intensive chemotherapy should be considered the best adjunctive treatment regimen for patients with node-positive breast cancer

In the age of precision medicine, chemotherapy remains the cornerstone
of breast cancer treatment.

Dose-intensive chemotherapy refers to chemotherapy with MTD or a smaller dose but a shortened interval between doses relative to traditional maximum tolerated dose (MTD) chemotherapy
once every 3 weeks.

Dose-intensive chemotherapy reduces recurrence and mortality
in patients with high-risk early-stage breast cancer.

The GIM2 study compared dose-intensive chemotherapy every 2 weeks with standard interval chemotherapy every 3 weeks, in a 2×2 factorial design, and the efficacy
of increasing fluorouracil as adjuvant chemotherapy for lymphnode-positive breast cancer in EC-P regimens.

Preliminary data analysis with a median follow-up of 7.
0 years showed that increasing fluorouracil did not improve efficacy, while dose-intensive chemotherapy significantly improved patients with DFS and OS
compared with standard interval chemotherapy.

This year's ESMO conference reported long-term survival analysis data
from the GlM2 study with a median follow-up of 15.
2 years.

The results showed that for patients with node-positive early-stage breast cancer, the increase in fluorouracil on the EC-P regimen did not improve DFS and OS
.

Dose-intensive chemotherapy had a significant benefit from both DFS and OS compared with standard interval chemotherapy, with an absolute benefit of 9% for DFS (61% vs 52%, P<0.
001) and an absolute benefit of 7% for OS (76% vs 69%, P<0.
001).

In addition, subgroup analyses showed that both hormone-positive and hormone-negative patients benefited
from dose-intensive chemotherapy regimens.

GlM2 studies have shown that dose-intensive chemotherapy should be considered the best regimen for patients with node-positive breast cancer and does not need to consider hormone receptor status
.

brief summary

In the 1970s, Professor Norton proposed the Norton-Simon hypothesis based on the Gompertzian curve: cancer cells proliferate faster in the initial stage of tumor growth, but when they grow to a certain volume, the proliferation rate of cancer cells will slow down; In chemotherapy, the rate of shrinkage of tumor volume is directly proportional
to the rate of tumor regrowth.

If the tumor cells are not completely killed, the volume doubling time of residual tumor tissue during the chemotherapy interval is shorter, that is, the residual tumor cells proliferate faster
than before chemotherapy.

If chemotherapy drugs are given early in the regeneration of tumor cells (that is, reducing the interval between treatment), a more significant killing effect can be achieved and the tumor cells
can be killed to the greatest extent.

That is, dose-intensive chemotherapy shortens the long time of tumor regeneration, acts on smaller tumors, and obtains a stronger total tumor killing effect
.

Therefore, the above hypothesis provides translational research ideas for the clinical application of dose-intensive chemotherapy ^regimens2
.

Long-term follow-up studies of GlM2 have shown that dose-intensive chemotherapy should be considered the best course of action for patients with node-positive breast cancer and does not need to consider hormone receptor status
.

However, in the use of dose-intensive programs, attention should be paid to toxicity problems, and patients should be fully communicated before treatment to do a good job in various prevention work
.

At the same time, combined with the patient's treatment tolerance, the population
that can receive a dose-intensive regimen is screened.

Bellini Research

Prospective prospect of neoadjuvant double-exemption for triple-negative breast cancer with TIL may be promising

Triple-negative breast cancer genome instability, high mutation load, and high levels of immune invasion are considered the most immunogenic subtypes of breast cancer, so patients with triple-negative breast cancer are more likely to benefit
from PD-1/PD-L1 inhibitors.

A series of clinical trials have been conducted on neoadjuvant immunotherapy for triple-negative breast cancer, such as the KEYNOTE-522 study with a PCR rate of up to 64.
8%.


The KEYNOTE-522 study on health-related quality of life (HRQoL) data was also updated at this ESMO conference, and pabolizumab also brought overall HRQoL ^{benefits to} patients under the premise of good
efficacy1.

In early-stage triple-negative breast cancer, high levels of tumor-infiltrating lymphocytes (TILs) tend to have a better
prognosis.

The BELLINI study is the first TIL-based neoadjuvant immunotherapy study for triple-negative breast cancer to date designed to evaluate the efficacy
of nivolumab + ipimumab in neoadjuvant therapy for early triple-negative breast cancer accompanied by TIL.

The results showed that after 4 weeks of neoadjuvant double exemption, the proportion of CD8-positive T lymphocytes and/or γ interferon expression multiplinations in the navuriumab + ipimumab group compared with the navuriumab group was 60% and 53.
3%,
respectively.

The overall safety is controllable, the incidence of grade 3 to 4 adverse events is 6%, the most common is hypothyroidism, and the two groups of adverse events are basically similar
.

Imaging evaluation found that the partial remission (PR) rates were 27% and 19%,
respectively, in the double exemption group and the single exemption group.

A total of 7 patients received PR, including 3 patients with high expression of TIL and 4 cases of
medium expression.

The TIL level in all PR patients is above 40%.


In addition, 24% of patients experienced complete clearance
of circulating tumor DNA.

BELLINI studies have shown that most patients with triple-negative breast cancer with TIL show increased immune activation after only 4 weeks of immunotherapy, and a significant proportion have a clinical response, highlighting the potential
of neoadjuvant immune checkpoint inhibitors without chemotherapy for triple-negative breast cancer.

brief summary

The BELLINI study suggests that our immune checkpoint inhibitors are more effective in a small proportion of patients with early-stage triple-negative breast cancer, and that the search for effective biomarkers to predict patients who are more likely to respond to neoadjuvant therapy with immune checkpoint inhibitors1
.

TIL is a promising biomarker in the immune microenvironment
.

In the IMpassion130 study, the degree of CD8+ T cell infiltration predicted OS benefit
when altelizumab was used in metastatic patients.

In the KEYNOTE-119 study, matrix TILs ≥ 5% predicted the benefit of pabolizumab, while Pabolizumab treated TILs≤5% of patients had a poor prognosis
.

In addition, the KEYNOTE-086 study showed that TILs were associated with immunotherapy ^efficacy3
.

At present, TILs have not been detected in conventional clinical practice, and it is worth looking forward to
in future explorations.

References:

1.
Ana Bosch，Breast cancer, early stage，Congress highlights，2022 ESMO.

2.
Professional Committee of Multi-Primary and Unknown Primary Oncology of Chinese Anti-Cancer Association.
Expert consensus on the clinical application of dose-intensive chemotherapy regimens of yew taxanes in China[J].
China Oncology, 2019, 29 (11): 910-920.

3.
Isaacs J, Anders C, McArthur H, et al.
Biomarkers of Immune Checkpoint Blockade Response in Triple-Negative Breast Cancer.
Curr Treat Options Oncol.
2021 Mar 20; 22(5):38.
doi: 10.
1007/s11864-021-00833-4.
PMID: 33743085.

Editor/Typesetting: Jiang Zhou

Execution: Small Garden