Cancer therapy is often associated with a weakening of the immunesystem. A weakening of the immunesystem is associated with a higher risk of infection, including a COVID-19 infection.

This additional risk needs to be taken into account when deciding on any cancer therapy.

Chemotherapy is considered to be the most important pillar of cancer therapy. One of the most difficult decision is whether chemotherapy should be performed in the absence of metastases, such as neoadjuvant or adjuvant chemotherapy. The aim of this approach is to improve the overall survival of the patient.  However, it is undisputed that "neoadjuvant chemotherapy confers risks of immunosuppression" (COVID-19 Pandemic Breast Cancer Consortium (USA)) thus leading to a weakening of the immune system.

1. Neoadjuvant chemotherapy

Neoadjuvant chemotherapy requires the start of chemotherapy to be ahead of surgery. This approach aims to reduce the size of the tumor and therefore creates a better basis for surgery. The original hope and expectation of destroying any existing micrometastases and thus improving survival did not realise. The long term outcome of neoadjuvant chemotherapy (before surgery) is roughly equivalent to adjuvant chemotherapy (after surgery) (1), but may lead to poorer results in some tumor subtypes (2). Nevertheless, the COVID-19 Pandemic Breast Cancer Consortium (USA) recommends neoadjuvant chemotherapy for patients with triple negative and Her2/neu positive breast cancer. When considering for or against such therapy, it should not be forgotten that triple negative or Her2/neu positive tumors which respond little or not-at-all to neoadjuvant chemotherapy have a particularly poor prognosis. ­ ­ ­ ­ ­ ­ ­ ­ It is currently in discussion, whether adjuvant chemotherapy should be added following the primary treatment (3). Breast cancer and other solid tumors do not have properties or markers that could predict whether the tumor will respond to a chosen treatment or if the tumor will be resistant. It is therefore an individual decision to go or not go ahead with the treatment. The option for this treatment should be decided in discussion between the patient and the treating physician.

The maintrac® testing of the chemosensitivity of circulating tumor cells (a cytotoxicity assay) can contribute to this discussion including the rationale for additional chemotherapy. In our basic and clinical research we were able to show that an in vitro no-response of the patient’s tumor cells circulating in the blood is correlated with a no-response clinically (measured as tumour reduction post therapy). The dynamic number of tumor cells in the blood is synchronous with the patient’s clinical response. It follows that the reactivity in the test tube predicts whether the tumor and tumour cells will respond clinically (a predictive marker) ­ ­ ­ ­ ­ ­ ­ ­

1 Adjuvant versus neoadjuvant chemotherapy in triple-negative breast cancer patients with BRCA mutations. Clifton K, Gutierrez-Barrera A, Ma J, Bassett R Jr, Litton J, Kuerer H, Moulder S, Albarracin C, Hortobagyi G, Arun B.Breast Cancer Res Treat. 2018 Jul;170(1):101-109. doi: 10.1007/s10549-018-4727-9. Epub 2018 Feb 22.PMID: 29470805

2 Neoadjuvant Chemotherapy Plays an Adverse Role in the Prognosis of Grade 2 Breast Cancer. Cancer. 2019 Sep 7;10(23):5661-5670. doi: 10.7150/jca.33168. eCollection 2019.PMID: 31737103 Zhu X, Xue J, Gu X, Chen G, Cao F, Shan H, Wang D, Qiao X, Liu C, Zhang Y.J J Cancer 2019 Sep 7;10(23):5661-5670. doi: 10.7150/jca.33168. eCollection 2019

3 Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes. Diana A, Carlino F, Franzese E, Oikonomidou O, Criscitiello C, De Vita F, Ciardiello F, Orditura M.Cancers (Basel). 2020 Mar 29;12(4):E819. doi: 10.3390/cancers 12040819.PMID: 32235297

2. Surgery

With respect to surgery, it is advised to postpone it temporarily unless it is essential. It is surprising to read from the COVID-19 Pandemic Breast Cancer Consortium (USA) the opinion that the high rate of clinical and pathological responses would allow a delay of the surgery. This is highlighted in the case of neoadjuvant chemotherapy.

However, it has been shown that delaying the surgical removal of the primary tumor is associated with a highly significant increased risk of local recurrences. This has been seen in patients with partial or complete resolution of the tumour following neoadjuvant therapy (pCR).

Patients with triple negative breast cancer have a particularly poor prognosis if residual tumour burden following neoadjuvant therapy has been diagnosed.

According to the COVID-19 Pandemic Breast Cancer Consortium (USA), surgery for hormone-receptor-positive tumors can be postponed without a negative effect on the prognosis. This patients can have endocrine treatment initiated ahead of surgery and thus have a much better prognosis.

Regular monitoring with maintrac® can be helpful. One of the main indication of the  maintrac® testing is the repeated analysis of the circulating tumor cells to monitor treatment effectiveness during endocrine therapy.

The COVID-19 Pandemic Breast Cancer Consortium (USA) with respect to Her2/neu positive tumours, is now recommending ado-trastuzumab emtansine to replace the previous treatment, the combination of trastuzumab and chemotherapy. We have seen good results in maintrac®  testing and clinical monitoring under this therapy. We approached previously the health insurers for reimbursement. This had been rejected at that time. Following the recent announcement by the Consortium, there is a good chance that this therapy will now be reimbursed by the health insurance companies.

A “watch and wait” approach is being considered for non-invasive breast tumors (DCIS) and low-activity prostate tumors (Gleason 6). Again, maintrac® can help to monitor these patients via the testing for circulating tumor cells. ­ ­ ­ ­ ­ ­ ­ ­

3. Adjuvant Chemotherapy

It is reasonable to question that patients with small or hormone receptor positive tumors do not benefit from chemotherapy (Stage 2 disease, including those with N1 nodal involvement, and those with low-intermediate grade tumors, lobular BCs, low-risk genomic assays or “luminal A ”signatures, do not benefit substantially from neoadjuvant or adjuvant chemotherapy).

This realisation is not new. The threat from the Covid-19 virus leads to preferences for other therapies. That means chemotherapy is no longer recommended as a matter of cause. The focus has shifted to endocrine therapy. For those patients, monitoring circulating tumor cells with maintrac®  can detect increased tumor activity early and provide the impetus for a more intensive.

4. Radiotherapy

Radiotherapy affects the immune system in a similar way, but not to the extent that chemotherapy does. We have shown that an increase of CTCs during radiotherapy is associated with an increased risk of recurrence. Anti-inflammatory drugs may inhibit corona-related inflammation as well as an increase in tumor cell count. During radiotherapy, it is the attendance at the treatment centres that may lead to infections. The time spent at a radiotherapy centre ought to be reduced as much as possible.

5. Immunotherapy

These therapies can have a major impact on the immune system. The extent to which it makes sense to start or continue such therapy under the current circumstances must be discussed between the patient and the therapist.

The new threat from Covid-19 and any planned tumor therapy should lead to an informed discussion between patients and therapists. All available measures should be taken to optimize a therapy and to minimize the ensuing risks.

Prof. Dr. med. Katharina Pachmann
Head of Research & Development ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­

maintrac® is an innovative analysis platform in cancer diagnostics and therapy monitoring. Maintrac identifies and quantifies the circulating tumor cells in the blood sample of cancer patients and analyzes the efficacy of selected drugs. In clinical trials with more than 900 patients, maintrac has demonstrated that monitoring circulating tumor cells in the adjuvant situation, during maintenance and antibody therapy in breast cancer has significant benefits. Possible relapses can be recognized at an early stage.

Further information:
www.maintrac.com ­ ­