Mönchengladbach – June 06, 2023
- The research of the award winners changes the reality of therapy
- Only 20% of women without lymph node involvement and only about 30% of women
(< 50 Jahre) mit ein bis zu drei befallenen Lymphknoten benötigen eine Chemotherapie - Need to catch up in clinical practice
professor dr Nadia Harbeck (Munich) and Professor Dr. Last Friday, June 2nd, 2023, Ulrike Nitz (Mönchengladbach) received the German Cancer Prize in the category Clinical Cancer Research awarded. Their research “has changed the reality of therapy for women with early breast cancer worldwide,” the jury explains its decision. The two physicians were honored for the two groundbreaking studies PlanB and ADAPT. They led these studies within the framework of the West German Study Group (WSG).
Less chemotherapy without worsening the chances of recovery
One in eight women will develop breast cancer in her lifetime[1]. Probably every woman in her life, herself or as a loved one, faces this disease. The diagnosis of breast cancer usually comes as a shock to those affected. Uncertainty as to which therapy is the right one and the prospect of possible chemotherapy trigger fears in many patients. About 70% of those affected will suffer from hormone-sensitive breast cancer. Antihormone therapy is prescribed for these women and the question always arises as to whether additional chemotherapy is necessary. Thanks to the work of the two German scientists, women with hormone-sensitive breast cancer and their doctors are now able to make the decision for or against chemotherapy with significantly more certainty and precision than was previously possible. In the justification for the award, the German Cancer Society points out that the studies will enable many patients to opt for chemotherapy-free therapy with little stress, without reducing the chances of recovery.
Multigene analysis and preoperative assessment of the success of antihormone treatment as key
A special feature of the studies is that the scientists included the genetic fingerprint of the tumor (PlanB). With the help of a multigene test, the so-called
Recurrence Score® Result determined. This value makes it possible to predict whether chemotherapy is required. In the follow-up study ADAPT, it was also tested before the operation how much success can be expected from the anti-hormone therapy. “Through this procedure, the number of chemotherapies among the study participants, especially in the group of
younger women (≤50 years) are significantly reduced,” says Prof. Dr. Ulrike Nitz.
46,000 women with hormone-sensitive breast cancer, but only 4,859 multigene tests performed – treatment reality and future
Around 46,000 women in Germany are diagnosed with hormone-sensitive (HER2) breast cancer with up to three affected lymph nodes every year[2]. It can be clarified individually for these women whether they really benefit from chemotherapy. Together with the American studies that used the identical multigene test and the work of the WSG, data are now available from almost
30,000 study patients. In summary and with the same wording, they show that multigene tests and anti-hormone therapy before the surgical removal of the tumor can save many women chemotherapy[3],[4],[5]. Another message that is important in everyday clinical practice is that when multigene tests are used, chemotherapy is recommended not only to a smaller number of women than with the conventional diagnostic criteria used up to now, but also to other women. The test can also be used to avoid potentially life-threatening undertreatment. This means that the treatment of a group of women whose risk is underestimated without the multigene test but who benefit from chemotherapy improves.
In summary, chemotherapy is justified and necessary for healing in about 20% of women without lymph node involvement and about 30% of women (less than 50 years of age) with one to three involved lymph nodes.3,4,5 For the other patients, chemotherapy-free therapy is required Treatment possible with excellent therapy success (provided that a short preoperative anti-hormone therapy was successful, especially in the young women).
In 2021, only 4,859 multigene tests were billed to health insurance companies[6]. According to surveys by Breast Cancer Germany eV, multigene tests are only offered to about a quarter of the women who are eligible[7].
The scientific results of the WSG studies have meanwhile found their way into the German and European treatment recommendations. “We hope that being awarded the German Cancer Prize will give the clinical implementation of our research results another significant boost,” said Professor Dr. nice
Attachments
Brief history of modern medical knowledge of breast cancer therapy
Therapy still “unselected” – chemotherapy in almost all patients
As early as the 1960s, it was recognized that breast cancer can be a “systemic” disease, which means that it spreads to the body very early on and can later develop into metastases. Therefore, the first system therapies – namely anti-hormone therapy and chemotherapy – were introduced at this time. Initially, these therapies were recommended to almost all patients.
Therapy already targeted
In the mid 90’s and 2000’s the hormone receptor and the HER2 receptor were discovered. The hormones estrogen and progesterone can affect the growth of breast cancer cells. They dock to binding sites (hormone receptors, HR) of the cell, which then transmit the growth signal into the cell interior. For tumor cells that require hormones to help them grow, withdrawing the hormones can slow or even stop tumor growth. It was quickly learned that anti-hormone therapy and anti-HER2 therapy only work if the corresponding receptor is formed on the tumor cell. This paved the way for targeted therapy.
The recommendation for chemotherapy applied if the woman was attested a risk of at least 10% of falling ill again within 10 years. From this stage it was assumed that the risk of the disease is higher than the risks from the chemotherapy itself. The risk assessment was made on the basis of tumor characteristics such as size and lymph node involvement, the age of the patient and the microscopically visible properties of the tumor. In many cases, however, these parameters do not allow an exact assessment of the risk of a recurrence. Therefore, in many cases, additional chemotherapy was recommended to be on the safe side – and thus incorrect and overtreatment was consciously accepted for lack of better evidence.
However, this therapy regime still has two weaknesses that every doctor is aware of:
- On the one hand, this risk assessment is not very precise and may be assessed differently in different laboratories.
- Second, high-risk breast cancer does not automatically respond to chemotherapy.
Therapy finally individualized
The hope of being able to use chemotherapy in a more targeted manner only germinated when the genetic fingerprints of the tumor could be taken. The 21 gene signature (Oncotype DX Breast Recurrence Score® test) was developed specifically for “hormone-sensitive” breast cancer, i.e. breast cancer whose growth is promoted by hormones, which promised a precise assessment of the risk and response of the tumor to chemotherapy. The 21 gene signature should first be tested in clinical studies to determine the extent to which it could help to control the use of chemotherapy in a targeted manner.
Two large studies with a total of more than 15,000 women started in the USA in the 2010s. Breast cancer patients with zero to three affected lymph nodes were included in the studies. In Germany, the West German Study Group (WSG), headed by the two award winners, started the PlanB study, which used the genetic fingerprint analogously. The follow-up study ADAPT also integrated the information from the result of a short preoperative anti-hormone treatment (endocrine sensitivity) into the decision about the further treatment concept. A total of around 30,000 women took part in the studies.
The German and American study results consistently show:
- Chemotherapy is not necessary in postmenopausal women if they belong to the approximately 80-85% with a low to moderate risk profile (as determined by genetic fingerprinting).
- This is also the case for young women with a low risk profile.
- With a moderate risk profile in the genetic fingerprint, the additional information from the preoperative anti-hormone therapy seems to be decisive. In the ADAPT study, women whose tumors are very sensitive to hormones have excellent chances of survival after 5 years without chemotherapy.
Of the approx. 70,000 new breast cancer cases in Germany every year, 60-70% of those affected suffer from what is known as hormone-sensitive breast cancer.
On the effect of chemotherapy
- Chemotherapy acts on every fast-growing cell – regardless of whether it is fast-growing healthy body cells or – usually even faster-growing – tumor cells. That explains the serious side effects on the immune system, hair, ovaries, etc. Chemotherapy is now carried out in Germany for 6 months as standard. It causes nausea, vomiting, hair loss, immunosuppression, irritation of the mucous membranes of the bladder and intestines, etc. Long-term side effects include numbness in the arms and legs (5 to 10%), heart failure (up to 10%), infertility in young women and, rarely, development new cancers. Many women become unable to work or can no longer cope with their everyday life as usual. These side effects make chemotherapy the most feared measure in breast cancer treatment.
The German Cancer Prize and breast cancer research
The prize of the German Cancer Society and the German Cancer Foundation is one of the highest honors in oncology and is awarded annually in the categories “Clinical Research”, “Translational Research” and “Experimental Research”.
Milestones in breast cancer research have already received several awards:
- In 1998, Axel Ullrich received the German Cancer Prize for his groundbreaking findings about a surface component of breast cancer cells – the HER2 receptor. The latter mediates the effect of the first antibody therapy (trastuzumab) developed against breast cancer. About 20% of today’s cases are HER2 positive (i.e. have this surface component) – still one of the clinically relevant subgroups today.
- In 2020, Rita Schmutzler was awarded the German Cancer Prize for the groundbreaking work of the Cologne working group on hereditary (familial) breast cancer (approx. 5% of cases) and its prevention.
[1] Robert Koch Institute: Status: 6/6/2023.
[2] Ortmann O. et al., Journal of Cancer Research and Clinical Oncology, 2023
[3] Sparano JA et al., New Engl J Med, 2018
[4] Kalinsky K. et al., New Engl J Med, 2021
[5] Nitz U et al. J Clin Oncol 2022
[6] Accounting statistics of the KBV, as of March 17, 2023
[7] Messinger D. et al., Future Oncology, 2023