Breast cancer is the hardest bone to chew, and the "Chinese solution" intends to treat it like this

Recently, a "Chinese solution" for the treatment of triple-negative breast cancer was published in a top global oncology journal. What is so special about triple-negative breast cancer? What results have been achieved so far?

Written by Lai Tianying (Medical and Health Group)

Editor/Feng Xiaohong New Media Editor/Chen Xuanzhi

Interview experts:

Zhang Jingxue (Director of Breast Surgery at Beijing Hepingli Hospital)

Recently, a "Chinese solution" for triple-negative breast cancer treatment was published in the Journal of Clinical Oncology, a top global oncology journal. It is reported that this result is expected to be included in the treatment guidelines and become the global standard for triple-negative breast cancer treatment.

▲The "Chinese solution" for triple-negative breast cancer treatment was published in the Journal of Clinical Oncology, a top global oncology journal (picture from China National Radio)

Subsequently, the U.S. Food and Drug Administration (FDA) also announced a piece of news about triple-negative breast cancer. It was reported that the FDA has approved the antibody-drug conjugate Trodelvy of the anti-cancer biopharmaceutical company Immunomedics, Inc. for marketing for the treatment of adult patients with metastatic triple-negative breast cancer.

(Image source: Screenshot of Immunomedics official website)

It can be seen that recent research results on triple-negative breast cancer have been remarkable, bringing hope to patients. For a long time, triple-negative breast cancer has been regarded as the toughest nut to crack in breast cancer. Under the general trend that breast cancer has gradually become "preventable and treatable", triple-negative breast cancer is still the goal of countless medical scientists and pharmacists, and many well-known pharmaceutical companies have also invested in the research and development of related drugs. What exactly is this "evil"? How insidious is it?

▎Triple-negative breast cancer knocks down anti-cancer heroes

"Those who have fallen must know that the earth is hard and dusty and can cause many cuts and bruises on people, but from another perspective, the earth also breeds beautiful flowers and gems." This is a passage from the story of Yan Hongwei, a cancer hero who recently died of triple-negative breast cancer.

Yan Hongwei is a young teacher at Shanghai University of Engineering Science. In 2004, she was admitted to a university in Nanjing from Shanxi Province. After graduating with a doctorate in 2011, she taught in Shanghai. After that, she and her husband took out a loan to buy a house, got married, and had children. Everything was fine at first, but fate played a joke on them and they got sick.

Yan Hongwei was diagnosed with advanced triple-negative breast cancer. Since then, Yan Hongwei has embarked on an arduous and arduous chemotherapy journey. She has endured unbearable pain in the chemotherapy room for 36 weeks out of 52 weeks a year. In order to cure her disease, she went to the United States for treatment and went to Hong Kong to buy unlisted targeted drugs. She tried almost all methods. Unfortunately, she failed to defeat the disease and died on March 18, 2019 after a year of fighting cancer. The news documentary "Human World" once recorded her anti-cancer story. Her death made people realize the danger of triple-negative breast cancer.

▲Anti-cancer hero Yan Hongwei (Photo source: Screenshot from the news documentary "The Human World")

▎Statistics tell you how serious breast cancer is

Data from the official websites of the World Health Organization and the National Institutes of Health in the United States show that cancer has become the leading "fatal killer" of humans worldwide. Among them, breast cancer is the type of cancer with the highest incidence rate except lung cancer. Some well-known women, such as Chen Xiaoxu, who played Lin Daiyu in the 1987 version of "Dream of Red Mansions", and singers Yao Beina and Asan, have all lost their lives to breast cancer.

For women, breast cancer has always been the most common disease. According to statistics from the World Health Organization's International Agency for Research on Cancer, in 2008, there were 1.38 million new cases of breast cancer in women worldwide, accounting for 22.9% of all female malignant tumors, and its incidence has continued to increase at a rapid rate in recent years. In addition, epidemiological surveys show that the incidence of breast cancer in China is about 160,000 people per year, and the mortality rate is about 120,000 people per year.

When interviewing Zhang Jingxue, director of the Department of Breast Surgery at Beijing Hepingli Hospital, the reporter learned that breast cancer has gradually become a "chronic disease" that can be prevented and treated. However, in the "big family" of breast cancer, the special subtype of triple-negative breast cancer accounts for about 15% of all types of breast cancer. It is of a high "level" and "notorious".

▎All three indicators are negative, no therapeutic target

According to breast surgery experts, the interior of a woman's breast is mainly composed of 15-20 glandular (mammary) lobules and adipose tissue. The glands are arranged radially, and their milk ducts face and open at the nipple.

The mammary gland is an accessory gland of the body, composed of skin, fibrous tissue, mammary glands and fat. It undergoes obvious age and functional changes under the influence of nerves and hormones. The mammary glands of pregnant women can secrete milk under the influence of prolactin, thus providing food for the baby.

▲Breast (Picture from the Internet)

The occurrence of breast cancer is closely related to the environment and lifestyle. It is rare in adolescent women and uncommon in women of childbearing age, but the incidence rate increases rapidly with age around the age of 45. About 70% of breast cancers worldwide occur in women over the age of 45, and the proportion of breast cancer patients in women over the age of 45 in my country is similar, accounting for 69.75% of all cases.

In the past, the medical community did not have a good way to determine the severity of breast cancer, and could only roughly assess it through the "TNM" staging system. T stands for the size of the tumor; N stands for regional lymph nodes (axilla, clavicle, and sternum); and M stands for whether there is distant metastasis. Based on this method, breast cancer is roughly divided into "early, middle, and late stages."

Later, scientists discovered that breast cancer has different biological behaviors and pathological characteristics. After surgery or puncture, patients undergo immunohistochemistry testing to determine the type of breast cancer based on the response of certain indicators. For example, if the estrogen receptor and progesterone receptor are positive, it is called hormone receptor-positive breast cancer; if the human epidermal growth factor receptor-2 (Her 2) indicator is positive, it is sensitive to targeted drugs and is called targeted-positive breast cancer.

If the three indicators of estrogen receptor, progesterone receptor and Her 2 are all negative, then this type of breast cancer is called triple-negative breast cancer, and its English name is TNBC. Since patients with these indicators are ineffective for Her2 targeted drugs and endocrine drugs, it is also called the non-target type.

Director Zhang said that currently, the disease is diagnosed clinically through mammography, biopsy, receptor and gene testing, etc. Its symptoms are similar to other types of breast cancer, mostly manifested as lumps or masses in the breast, breast pain or redness, nipple inversion or discharge.

This disease is highly malignant, invasive, and prone to metastasis. Studies have shown that the rate of organ metastasis in patients with triple-negative breast cancer is higher than that in patients with non-triple-negative breast cancer, and the rate of metastasis to the lungs and brain is also higher than that in patients with non-triple-negative breast cancer. It is also prone to recurrence, which is a "long-standing" problem in the field of breast cancer treatment, and the prognosis is very poor.

Relevant experts pointed out that its cancer cell proliferation index is relatively high and problems are most likely to occur within three years after surgical treatment. It is for this reason that it is "notorious."

▎Scientists are still exploring "therapeutic tools"

As mentioned above, triple-negative breast cancer has no targets, so breast surgery experts say it is not sensitive to endocrine therapy and molecular targeted therapy, unlike other types of breast cancer, which have many treatment options. For example, patients with positive targets can be treated with targeted drugs (dual-target or single-target) for one year; for another example, patients with positive endocrine disease can receive endocrine therapy for 5-10 years.

The only systemic treatment for triple-negative breast cancer is chemotherapy. "For breast cancer, a comprehensive treatment is usually adopted, including surgery, chemotherapy, radiotherapy, targeted therapy, endocrine therapy, etc. For triple-negative breast cancer, the test results of estrogen receptor, progesterone receptor and HER-2 are all negative, so the only treatment after surgery is chemotherapy. Even in the late stage, there is only chemotherapy." Director Zhang emphasized.

Some experts also said that the international community is particularly cautious about the treatment of triple-negative breast cancer. Except for very special triple-negative cases, basically as long as the tumor is larger than 5 mm, even if there is no lymph node metastasis, chemotherapy is often required.

(Picture from the Internet)

After surgical treatment, patients with early triple-negative breast cancer usually need adjuvant chemotherapy based on anthracyclines and taxanes. During the treatment process, the standard adjuvant chemotherapy regimen has been verified to be effective through multiple clinical trials. The Guidelines and Norms for Diagnosis and Treatment of Breast Cancer of the Chinese Anti-Cancer Association (2017 Edition) suggest that the preferred chemotherapy regimen for triple-negative breast cancer is a dose-density regimen containing taxanes and anthracyclines; for recurrent and metastatic advanced triple-negative breast cancer, the guidelines state that gemcitabine plus carboplatin or cisplatin can be selected.

However, due to the complex heterogeneity of triple-negative breast cancer, the 5-year survival rate of patients receiving such traditional chemotherapy regimens has long hovered around 80%. In order to overcome this "hard nut to crack" in the field of breast cancer treatment, experts have launched various attempts and explorations.

At the 2017 American Society of Clinical Oncology, a study conducted by the Abramson Cancer Center at the University of Pennsylvania showed that a targeted drug called Olaparib (a drug targeting a known cancer-causing site) has a good effect in treating breast cancer with gene mutations and can better improve the survival rate of such patients. Professor Zhang Jin of Tianjin Medical University Cancer Hospital also said: "This drug has the potential to become a new treatment for triple-negative breast cancer."

Currently, Olaparib is available in China, but its approved indication is ovarian cancer. Professor Zhang Jin said: "A phase III multicenter trial of Olaparib for triple-negative breast cancer with gene site mutations has been carried out in China. Olaparib is currently used as the first-line treatment for advanced triple-negative breast cancer, i.e. recurrent or metastatic triple-negative breast cancer. Whether Olaparib can be combined with postoperative adjuvant therapy for triple-negative breast cancer to prolong survival is also under clinical research."

▲Olaparib is suitable for patients with triple-negative breast cancer with gene site mutations (picture from the Internet)

At the 2018 American Society of Clinical Oncology, a German study showed that adding Durvalumab (an immunosuppressant) to the neoadjuvant treatment of primary triple-negative breast cancer can relieve related symptoms in patients. Durvalumab has shown good efficacy in bladder cancer and lung cancer. This study explored the neoadjuvant treatment of Durvalumab combined with the taxane-anthracycline chemotherapy regimen, and a total of 174 patients were enrolled in the study. The results showed that patients had good tolerance (a state in which the body's responsiveness to drugs is reduced) after adding Durvalumab. Researchers believe that neoadjuvant therapy with the addition of Durvalumab may bring benefits, and the specific effects need further study.

It is understood that many pharmaceutical companies are also conducting research on Durvalumab and plan to recruit patients with triple-negative breast cancer in the hope that this drug treatment can achieve greater benefits.

On March 8, 2019, the FDA approved the world's first immunotherapy for triple-negative breast cancer, Atezolizumab. Researchers combined Atezolizumab with albumin-bound paclitaxel to treat patients with advanced or metastatic triple-negative breast cancer. The approval of this combination therapy provides good news for later studies on the treatment of triple-negative breast cancer.

▲FDA accelerated approval of the world's first drug for immunotherapy of triple-negative breast cancer (Image from CNN)

Director Zhang said that the research on targeted therapy and immunosuppressants is commendable, but they are still in the exploration process and have not yet been applied in clinical practice. However, it is believed that scientific research exploration will provide a continuous source of power for the ultimate cure of triple-negative breast cancer patients.

▎Can the "Chinese solution" and new American drugs bring good news?

The "Chinese solution" for triple-negative breast cancer treatment was led by Professor Shao Zhimin, director of the Department of Breast Surgery at the Affiliated Cancer Hospital of Fudan University. The researchers spent eight years working hard to come up with this result.

Professor Shao Zhimin said that for patients with early triple-negative breast cancer, postoperative adjuvant chemotherapy based on anthracyclines and paclitaxel drugs is the standard treatment option. However, the 5-year survival rate of patients is still hovering around 80%, which has become a "bottleneck" of survival rate. According to statistics, the 5-year survival rate of patients with other types of breast cancer is 83.2%. In comparison, the survival rate of patients with triple-negative breast cancer is indeed not optimistic.

Professor Shao Zhimin believed that the combination of clinical drugs such as anthracyclines and paclitaxels with capecitabine as adjuvant chemotherapy could achieve significant therapeutic effects for patients with triple-negative breast cancer. Therefore, he organized a nationwide multicenter clinical trial in 2012.

▲The first author Professor Li Junjie (left) and the corresponding author Professor Shao Zhimin (right) (Image from Science World)

Over the past eight years, Professor Shao Zhimin's team has successfully enrolled and treated 585 patients in 35 centers across the country. The patients were randomly divided into two groups, of which 297 patients in the experimental group received a traditional treatment combined with capecitabine, while the control group received a traditional chemotherapy regimen.

Director Zhang said that according to her understanding, the "Chinese solution" for treating triple-negative breast cancer has increased the five-year survival rate of patients from 80.4% to 86.3%, an increase of about six percentage points. The risk of recurrence was reduced by 41%, the risk of distant metastasis was reduced by 37%, and the overall survival rate was increased by 2.6%, greatly improving the prognosis of patients.

▲ Capecitabine significantly increased the 5-year survival rate of patients (Picture from Qidian.com)

Professor Shao Zhimin said: "We are also pleased to see that after combined capecitabine treatment, patients tolerated it well, the incidence of adverse hematological events was comparable to that of the control group, and there was no additional adverse reaction that patients could not tolerate during treatment."

At the same time, Professor Shao Zhimin also said that the breast cancer research team of the Affiliated Cancer Hospital of Fudan University has drawn the world's largest genetic map of triple-negative breast cancer, and future treatment strategies will also "go hand in hand" with this research, hoping to achieve greater breakthroughs in early breast cancer.

Let's talk about Trodelvy, which was approved by the US FDA. Trodelvy is the first FDA-approved targeted drug for treatment and the first drug approved for marketing by Immunomedics, Inc. in its 37 years of establishment. It brings good news to adult patients with metastatic triple-negative breast cancer.

The clinical trial included 108 patients with metastatic triple-negative breast cancer who had received at least two treatments for metastatic disease before receiving Trodelvy. Its efficacy is judged based on the total response rate data, which reflects the percentage of patients whose tumors have shrunk. Trodelvy achieved a total response rate of 33.3% in the trial, with a duration of response of 7.7 months. Among patients who responded to Trodelvy, 55.6% of patients had a duration of response of more than 6 months, and 16.7% of patients had a duration of response of more than 12 months.

"The approval of Trodelvy will provide physicians with a new tool to treat this disease," said Aditya Bardia, director of precision medicine at the Massachusetts General Hospital Breast Center and one of the lead investigators. "In the trial, Trodelvy demonstrated clinically meaningful responses in patients with refractory metastatic triple-negative breast cancer."

However, the FDA reminds that the use of this drug may lead to the risk of severe neutropenia and diarrhea, as well as adverse reactions such as hair loss, nausea, fatigue, anemia, vomiting, constipation, loss of appetite, rash, abdominal pain, etc. Therefore, it is necessary to strictly follow the doctor's instructions.

References:

[1] FERLAY J, SHIN HR, BRAY F, et al. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 Internet. Lyon, France: International Agency for Research on cancer; 2010

[2] Yuan Yewei. Latest treatment and research progress of triple-negative breast cancer[D]. 2015.

[3] Gao Lanxiang, Yang Guangzhi, Ding Huaye, et al. Observation of pathological morphology of basal cell-like invasive breast cancer[J]. Chinese Journal of Pathology, 2008, 037(002):83-87.

[4] Fudan University News: "The Affiliated Cancer Hospital Releases the "Chinese Solution" for the Treatment of Triple-Negative Breast Cancer"

[5] China National Radio: "The 'Chinese Solution' for the treatment of triple-negative breast cancer is the first in the world, with a 5-year disease-free survival rate of 86.3% and a 41% reduction in the risk of recurrence"

[6] Sohu News: "The world's first! FDA approves targeted ADC drug for metastatic triple-negative breast cancer to accelerate market launch"

https://www.sohu.com/a/390541292_120054371

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