Inclusion of adjuvant chemotherapy in luminal breast cancer

Bookmark and Share
Published: 15 Jul 2013
Views: 4965
Rating:
Save
Dr Marco Colleoni - European Institute of Oncology

Dr Marci Colleoni talks to ecancer at MBCC 15 in Milan about the threshold for the inclusion of adjuvant chemotherapy in luminal breast cancer.

Dr Colleoni discusses trials that will take place in order to determine an answer to this question as well as others regarding adjuvant treatment and recurrence.

15th Milan Breast Cancer Conference

Inclusion of adjuvant chemotherapy in luminal breast cancer

Dr Marco Colleoni - European Institute of Oncology


One of the major unsolved questions is still the threshold for the inclusion of adjuvant chemotherapy in luminal breast cancer. Trials currently have failed to reach an adequate number of patients in order to answer this question. It is possible that several trials in the future will adequately answer this problem, this question, to this issue. In fact, we have the MINDACT study in node negative, 1, 2, 3 positive axillary nodes that already concluded the accrual of the patients. We have also the ReSPONDER trial in the node positive population and also another trial in the node negative population trying to answer the question of chemo versus no chemo in the population with an intermediate Oncotype DX risk score. However, these data are not available today and meanwhile the recent St Gallen consensus conference decided to restrict the definition of luminal B breast cancer in order to properly identify those patients that are at high risk for recurrence. Now the patients that are classified as luminal B HER2 negative are those with the ER positive disease or two negative disease and any of the following which means high Ki-67, low or no expression of PgR and, if available, with a high multi-gene expression profile expression. The luminal B HER2 positive subgroup includes those patients that obviously had ER positive disease but also HER2 positive disease, irrespective of the Ki-67 or PgR expression. So I believe that the news is that the role of PgR now that the cut-off has been selected close to 20% according to a recently published study for identification of a subgroup of patients that despite being possibly luminal A have a worse prognosis.

The second point relates that it was confirmed the rule of Ki-67, although the proper cut-off has not yet been established because we have a node study, a single study that identified patients at higher risk with a cut-off of 14%. But it’s possible that a higher cut-off, let’s say 20%, might be more appropriate for the identification of high risk patients.

One of the news is the rule of multi-gene expression profiles because now it was acknowledged the fact that these multi-gene profiles are more precise in the definition of subtypes as compared with standard immunohistochemistry.

So these are the main news. Regarding the treatment, most of these patients with luminal B disease should receive obviously endocrine therapy but also chemotherapy. When chemotherapy is prescribed it should contain anthracyclines and taxanes and should be administered for at least six courses although there are some controversies about these issues. This is related to the fact that studies in the past did not focus on specific therapies on a specific subgroup of patients so we have no information on which type of chemotherapy precisely for luminal B disease. There is  no specific regimen identified and also when we decide to prescribe the chemotherapy we should always take into consideration the preferences of the patient as well as the comorbidity, desires of pregnancy, desire to avoid alopecia, for example, so all these items should be taken into account in the therapeutic algorithm.

Regarding the subgroup of luminal B HER2 positive disease, there are no particular news since there are no data supporting avoiding chemotherapy within this subgroup of patients. So treatment should include anti-HER2 therapy, endocrine therapy and cytotoxics. This is related to the fact that all the trials in the past included also chemotherapy , anti-HER2 therapy and also the fact that if you look at the management of the effect within trials there is no evidence of a different effect, for example between ER and PgR positive disease and ER and PgR negative disease if HER2. So there are no news for these patients.

In conclusion it was confirmed this year that luminal B disease represents a more aggressive disease, less endocrine responsive and correlating with a worse prognosis. It was refined the definition of these tumours. It was acknowledged the fact that multi-gene expression tests might properly identify this subgroup of patients with luminal B disease versus luminal A, those who require chemotherapy versus not although it was acknowledged also the fact that this test will not be available for the majority of the patients within the next months or next years. So it is possible that future trials will address, or better address, the question of which patients should be candidates for chemotherapy plus endocrine therapy versus endocrine therapy alone but meanwhile a proper use of available immunohistochemistry analysis, including ER, PgR, Ki-67, HER2 for clinical purposes are useful for our patients. However, in our decision again we should take into consideration the preferences of the patients as well as comorbidities and all the factors that should guide us for a tailored approach to the patient.