Source 丨 Cancer Channel in the Medical Circle
Three -negative breast cancer (TNBC), doctors who hear this diagnosis will almost frown. Compared with other subtypes, it has less treatment. Chemotherapy is the only effective treatment method.
This special subtype, because of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), all are negative expression, which makes doctors unable to start.
What matters worse is that triple-negative breast cancer accounts for 10%-16%of all breast cancer. The age of onset is smaller than that of TNBC. Local recurrence and long-distance metastases are high, and the mortality rate is high. At present, there is no treatment guide for TNBC systems. Chemotherapy plan, which drug is more sensitive to reaction to triple -negative breast cancer …
Three -negative breast cancer is so “hated”, is no one who really “rectifies” it?
The use of targeted drugs may not be far away
1. PARP inhibitor
At the 2017 American Clinical Oncology Society (ASCO), a phase III clinical trial of the University of Pennsylvania’s Aubramson Cancer Center showed that a targeted drug called Olapani was treating HER2 negative metastatic breast cancer and BRCA The mutant breast cancer is significantly better than standard chemical, which can better improve the no progressive survival period of such patients. Researchers believe that Olapani may be used for BRCA mutations and three -negative breast cancer patients.
“Indeed, this drug is hoped to become a new treatment method for three -negative breast cancer.” Professor Zhang Jin of Tianjin Medical University Cancer Hospital said that, in fact, Olapani has been listed in China, but the approved certificate is ovarian cancer.
Don’t worry, Olapani’s phase III multi -center test for the three -negative breast cancer of BRCA1 mutations has been carried out in China. Essence
Professor Zhang Jin said that the current follow -up is the first -line treatment of Olapani for advanced three -negative breast cancer, that is, recurrence or metastasis tri -negative breast cancer; Olapani, extending the disease -free survival period, is also in clinical research.
2. AKT inhibitor
In three negative breast cancer, the PI3K/AKT signaling pathway is often activated due to the PIK3CA or AKTI mutation and Penti-3 changes. Three-negative breast cancer is often accompanied by the lack of PTEN and is related to the AKT pathway activation. Researchers then tried to apply AKT inhibitors.
2018 ASCO reported this study: Azd5363 (Capivasertib) combined with paclitaxel control agent combined with paclitaxel first -line therapy metastatic triplet breast cancer.
This is the phase II clinical trial (PAKT research) of random, double -blindness, and placebo control, and concluded that Capivasertib used to use cancer patients (such as advanced breast cancer, lung cancer, prostate cancer, gastric cancer, etc.) in the past Not ideal. If combined with genetic mutations, the efficacy will be significantly improved.
The other item is: iPatasertib combined with paclitaxel first -line treatment of local advanced or metastatic triplet breast cancer patients.
Ipatasertib is a high-selective Pan-AKT inhibitor that targeted AKT1/2/3. The study reported at the 2017 “Lancet Oncol” that the results of the non -progressive survival (PFS) results of the main research end point: 6.2 and 4.9 months, respectively.
The total survival period of the iPatasertib group (OS) was significantly higher than the paclitaxel group (23. January vs. 18. April), and supported the ongoing phase III clinical trial.
The AKT inhibitor is in the early stage of research and development. It is currently not officially approved to be applied to the clinic, but the data is encouraged.
Looking forward to the targeted drugs, let’s take a look at the immune inhibitors that have been hot these years. Will it be the next possibility of breaking through the treatment of three -negative breast cancer?
2018 ASCO: What does the immunosuppressant in TNBC research explain?
A lot of immunoscopic agents have been listed abroad. This year, China has also approved the first immunosuppressor to target lung cancer. Immune tumor treatment has entered China’s lung cancer in unstoppable trend, and can breast cancer be far away?
This year ASCO’s report on triple -negative breast cancer, immunosuppressives. In some immunothe check point inhibitors In advanced and early three-negative breast cancer, PD-1/L1 antibody response rates are higher during combined with chemotherapy. E.g:
From Germany, a random and phase II study shows that Durvalumab (an immunosuppressant) can be added to the new triple -negative breast cancer therapy in primary trice -negative breast cancer. ), But the PCR rate is significantly higher in the preset sub -group. (Durvalumab is used for IM subtypes for tri -negative breast cancer).
Durvalumab is a PD-L1 antibody, showing a better curative effect in bladder cancer and lung cancer. This study is a new assisted treatment of Durvalumab on the basis of the purple shirts of triple-negative breast cancer-pyromone chemotherapy schemes. It studied a total of 174 patients with triple-negative breast cancer in a total of 174 cases of tumor infiltration lymphocytes (low/medium/medium/medium/medium/medium/medium. High) layered. In the research conclusion, the PCR rate is significantly higher in the sub -groups of the following preset: (1) patients using Durvalumab before chemotherapy (61.0% vs 41.4%);
(2) Phase IIA and higher staged TNBC patients (55.4% vs 38.6%);
(3) Patients less than 40 (69.2% vs 42.9%).
In addition, the patient tolerates the patients after adding Durvalumab. Researchers believe that neo -assisted therapy joining Durvalumab may bring benefits, and further research needs to continue.
Another study is DURVALUMAB combined with white protein paclitaxel sequential dosage dosage dosage dense glycotoxycin and cyclopensimam new -assisted treatment of triple -negative breast cancer. No dose restrictions were found in the stage I study, and the recommended dose of stage II was 10mg/kg.
Conclusion shows that Durvalumab (10mg/kg, Q2W)+NP preface DDAC solution is tolerable; in the mid -term analysis, the PCR rate reaches 60%, which is equivalent to the PCR rate of the NP sequence DDAC scheme in the SWOG S0800 study. Note.
However, this is a single-arm study that does not compare the head opposite with the single-use chemotherapy (NP-DDAC). More studies are still required to confirm the results of this study.
At present, several immune examination point inhibitors show the following results:
In the future, it is necessary to accurately screen patients who can benefit and properly handle the adverse reactions of immunotherapy.
Chemotherapy must be made good
New drugs are worth looking forward to, but chemotherapy is still the only effective treatment method at present, and it must also do full homework on available drugs.
Clinically, the conventional treatment scheme of breast cancer is treated in the treatment of triple -negative breast cancer. Most of the newly adjusted chemotherapy programs and rings are mostly adopted by the auxiliary chemotherapy schemes. “Guidelines and Specifications for Breast Cancer Diagnosis and Treatment of the China Anti -Cancer Association (2017 Edition)” reminds that the preferential chemotherapy scheme of tri -negative breast cancer is a dose density scheme containing purple shirts and rings; Jesitabin plus card platinum or cisplane.
Most three -negative breast cancer has a deficiency or mutation of BRCA1, which is extremely sensitive to drugs that can destroy DNA structures, such as alkylated agents, fillemillin C, platinum drugs, foot leafylidin, and boromycin. Therefore, the method of treating BRCA1 -related tumors is also suitable for those who have lost or lack of breast cancer BRCA1 function.
These clinical experience may be beneficial to patients
Three -negative breast cancer is difficult to deal with, biological characteristics must be very special, and individualization is largely based on rich clinical experience.
Professor Zhang Jin shared some experience:
1. Three -negative breast cancer lymph nodes are positive, and patients with high lymph node metastasis can appear in the clock.
Studies from the Tianjin Medical University Cancer Hospital show that the prognosis of triple -negative breast cancer is related to age, family history, tumor size and armpit lymph nodes, suggesting that the age of the onset of the onset, the large primary tumor, the family history of breast cancer, and the positive prognosis Poor, among which the axillary lymph nodes and tumor size are its independent prognosis factor.
2. Reproduction and transfer time have characteristics. Three-negative breast cancer will have recurrence and metastasis earlier, but if the first 5 years will be spent, the recurrence risk of 5-10 years or even 10 years may be consistent with other types.
DenT et al. During the 5-year follow-up, the distant metastasis rate of triple-negative breast cancer was significantly higher than that of non-triple-negative breast cancer (33.9% vs 22.4%). The peak appeared, and then decreased rapidly. At 5 years, the risk was low. No distant transfer was found in 8 years later.
3. Due to different biological behaviors, the characteristics of cancer cells are different, the target of metastasis of tri -negative breast cancer is more special, and more of them are brain metastases and internal organs. Non -three -negative breast cancer is more common in bone metastasis and soft tissue metastasis.
4. There are differences in follow -up. Brain tissue is not a multiple metastases, not a required organs for breast cancer follow -up. There are no differences in the follow -up process and time cycle of various types of breast cancer.
5. In terms of radiotherapy. Axillary lymph nodes, the size of the mass, and the molecular type are radiotherapy reference indicators. Sanyin breast cancer is highly sensitive to radiation. When evaluation cannot be fully confirmed whether radiotherapy is performed, radiotherapy may be selected if it belongs to tri -negative breast cancer.
If there are 1-3 lymph node metastasis with lymphatic tumor thrombus, positive receptor, and limited to the outer group, you can do not take radiotherapy;
On the contrary, 1-3 lymph nodes are accompanied by high value-added index, KI67 high, and relatively large mass, usually radiotherapy.
“Three -negative breast cancer is a type, not a certain molecular typing, which is generally considered by the academic community. If you want to win strangely, only preciseFurther exploration. “
Professor Zhang Jin said that from August 16-18, the third Asian breast cancer conference · 2018ASCO overseas venue and the eleventh Tianjin International Breast Cancer Conference will be held in Tianjin.Make a detailed report.
According to Professor Zhang Jin, the executive chairman of the conference, the theme of this conference was precise diagnosis and treatment. Invited international digital top experts in the United States, Japan, and South Korea, and the country including Taiwan, Hong Kong, including Taiwan, Hong Kong, etc.Well -known experts, they will bring reports representing the world’s most advanced breast cancer diagnosis and treatment.