Breast cancer is one of the most common types of cancer. Around 13 out of 100 women will develop it in the course of their lives. The chances of survival vary considerably depending on the type of tumor and stage. Yet the chances of a cure are getting better and better thanks to new medicines and therapies. One real beacon of hope comes in the form of so-called antibody–drug conjugates, or ADCs.

(Published: January 2025)

Medical teams at Helios Hospital Berlin-Buch have used this innovative therapy in breast cancer patients in the context of a global long-term study – with great success. The results of the study – which was given the name KATHERINE – were recently published in the renowned New England Journal of Medicine (NEJM). The NEJM is one of the most respected scientific journals in the world, only publishing scientific papers that have never previously been published.

Prof. Michael Untch is chief physician in the gynecology and obstetrics department at Helios Hospital Berlin-Buch and head of the certified centers for breast cancer and gynecological cancers. He has been researching antibody therapies used in the treatment of breast cancer for over 30 years and played a key role in designing, conducting, and evaluating the study.

Professor Untch, around 1,500 women from all over the world with breast cancer took part in the study, which was launched ten years ago. You treated some of them in Berlin-Buch. What conclusions do you draw from the study results that have now been published and what do you consider to be the most important finding?

Prof. Michael Untch: Ninety percent of the women who were given an antibody–drug conjugate are still alive ten years later. They have not experienced any disease recurrence, or relapse, and they have not developed any metastases. And these are women who had suffered from a particularly aggressive type of breast cancer.
 

In other words, the treatment has helped patients who were previously at a higher risk of disease recurrence? 

Prof. Untch: That’s right. Despite conventional chemotherapy and antibody therapy and subsequent surgery, the patients in the study still had vital tumor tissue – that is to say, tissue capable of growth – in the breast or lymph nodes. In nine out of ten patients who received the ADC treatment for a year, breast cancer is no longer detectable, representing a real revolution in treatment. This promising therapy can give many patients new hope.

How do you explain the tremendous effect of these ADCs?

Prof. Untch: In our study, we administered a new ADC known as “trastuzumab maytansine” by infusion. We use it to transport a highly potent cancer drug to the cancer cells in a very direct and precise manner. Chemically, every ADC medicine is composed of three elements: a so-called monoclonal antibody, then the actual drug, the cytostatic agent, also known as the payload, which is designed to fight and destroy the cancer cell and neighboring cancer cells, and a so-called linker, which connects both substances. It only works when the conjugate is in place and docks onto a cancer cell. The cancer drug is thus connected to the monoclonal antibodies using innovative linker technology. These antibodies consist of proteins and are able to locate certain proteins on the surface of tumor cells and dock onto them. What is particularly special about this is that the new ADCs enable a much more targeted and thus highly effective form of therapy to be administered.

What exactly is the role of these tumor proteins?

Prof. Untch: These are so-called receptor molecules known as HER2. They work like antennae on the cell surface and transmit growth signals to the tumor cell. Such receptor molecules are now also known in other cancers. For example, we are aware of Trop-2, Claudin-6, and folate receptor alpha.
"In nine out of ten patients who received the ADC treatment for a year, breast cancer is no longer detectable.And the ADC medicine finds the right target on its own – in other words, the receptor molecules on the tumor?

Prof. Untch: Exactly. And this allows us to use very strong therapeutics in ADC therapy because they attack far fewer healthy body cells. 

ADC therapy is not suitable for every type of cancer. How do you establish which patients you can help with ADCs? 

Prof. Untch: We start by taking a sample of tumor tissue to see if we can detect the aforementioned HER2 molecules on the cancer cells. This applies to around 25 percent of tumors in the case of breast cancer. In 15 to 20 percent of cases, there are a particularly large number of molecules – then we speak of so-called HER2 overexpression. In such patients, we were able to significantly improve the prognosis with ADC therapy – both in the advanced and early stages, as our study has now shown.

Is the treatment very complex? 

Prof. Untch: No more complex than any other form of therapy. The ADCs are manufactured by pharmaceutical companies and dosed for each patient in our in-house pharmacy before being administered via infusion by our specialist staff. This is almost always done on an outpatient basis. However, we doctors must always look out for possible new side effects. 

What kind of side effects are we talking about?

Prof. Untch: ADCs are powerful medicines. And although they work in a highly targeted manner, they are not as nontoxic as we would have liked. This means that we definitely see side effects even with this form of therapy. In the study, for example, we observed lower platelet counts in the blood as well as some other side effects. However, they are not as severe as those associated with typical chemotherapy. The side effects of the newer ADCs – such as the “trastuzumab deruxtecan” – can include nausea and vomiting. These are symptoms that are similar to those seen in classic chemotherapy and can be managed well with medication. Particularly where the latest generation of ADCs are concerned, however, we have to watch out for completely new side effects, such as so-called interstitial lung disease or side effects on the cornea.

Can ADCs be used in the first instance – thereby saving patients from having to undergo classic chemotherapy?

Prof. Untch: We are actually running studies at the moment to trial the use of ADCs from the very beginning. Even as a substitute for classic chemotherapy. However, we are only expecting to see results in the coming years. 
 

It can be very hard for patients to go through chemotherapy. How important is it for patients to play their part in the treatment?

Prof. Untch: The so-called compliance of patients also plays a very important role in therapy involving ADCs. In order to comply with the therapy recommendations, the therapy plan should be explained to the patients in detail, along with its advantages and side effects, and close monitoring should also be discussed. Cancer therapy that is designed to lead to a cure always involves not only administering a brief, short-term treatment, but also being prepared for long-term monitoring over a period of ten or more years. This calls for a great deal of stamina.

Are ADCs also suitable for treating other types of cancer? 

Prof. Untch: Around 400 ADCs are now in development, which are being used to treat a wide range of malignant diseases. Not just breast cancer, but also ovarian, endometrial, and cervical cancers.

Professor Untch, what in your view is the next major milestone in cancer therapy?

Prof. Untch: We are currently seeing a real race between two therapeutic approaches: ADCs on the one hand and tumor vaccines – that is to say, special vaccinations against cancer – on the other. The outcome remains to be seen, but one thing is already certain: By detecting breast cancer at an early stage through mammography screening and using various improved drug therapies – in the case of breast cancer, these are the CDK 4/6 inhibitors, PARP inhibitors, or selective estrogen receptor degraders, or SERDs – we can offer more and more patients the prospect of a cure.

Further information

The long-term study known as “KATHERINE” was recently published in the renowned New England Journal of Medicine: Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer 

Further information about the world’s biggest conference on the subject of breast cancer treatment: San Antonio Breast Cancer Symposium

Prof. Michael Untch recently took part in a panel discussion as part of the San Antonio Breast Cancer Symposium 2024. You can find a series of short expert interviews on the subject of breast cancer here: SABCS 2024 | Round Table Breast Cancer Germany e.V.