Some information about breast cancer and check point inhibitors..
Professor Peter
Schmid, FRCP, MD, PhD
Featuring an interview with Prof Peter Schmid. Published August 2025.
Related links:
Home
Post-test
CE information and faculty disclosures
Select publications
PowerPoint slides
Download audio program
Companion video interview
Companion video lecture
Response to immunotherapy in breast cancer subtypes
DR LOVE: Welcome to “Oncology Today: Optimizing the Management of Metastatic BRCA-Negative, Triple-Negative Breast Cancer.” This is medical oncologist Dr Neil Love. For this program, I met with Prof Peter Schmid from Barts Cancer Institute in London. In addition to this interview, there is also a corresponding video program featuring Prof Schmid’s slide presentation.
To begin, I asked him to discuss the immunogenicity and potential response to checkpoint inhibitors that’s seen in breast cancer compared to other solid tumors.
PROF SCHMID: Yeah, a really important question. So breast cancer in general, and it’s always difficult to generalize, is less immunogenic compared to obviously melanoma but also lung cancer and some of the more squamous type diseases. But of course within breast cancer, such a wide and heterogeneous disease, there are some subgroups that have a high tumor mutational burden, high mutational load. Triple-negative breast cancer has probably the lowest-hanging fruit, but we equally see a group of patients with HER2-positive breast cancer who have a high mutational instability and therefore many neoantigens, and even in luminal B cancers in ER-positive breast cancer we probably have many tumor antigens and could consider that.
I would expect, and if you look at some of the data, the early studies, for example, in HER2-positive breast cancer, we saw actually interesting signals that were very similar to TNBC. We have seen in early ER-positive breast cancer, again in the neoadjuvant studies, a very powerful signal for the addition of immune therapy.
What is clear is the percentage of patients who may benefit from immune therapy is probably higher in TNBC compared to ER-positive breast cancer, but if you select the right patients, and we need to be more proactive in breast cancer compared to other tumor types to find the right patients who may benefit from immune therapy, and that group is small in ER-positive breast cancer, but still a group where I would expect immune therapy to work in the future.
At the moment PD-L1 seems to be, despite all the limitations, the best marker we have to select those patients. And PD-L1 in breast cancer is very different to for example lung cancer. In lung cancer, in a substantial proportion of patients, PD-L1 expression is found on cancer cells. In breast cancer most of the PD-L1 expression is actually on the immune infiltrate, and as such there’s a big overlap between PD-L1 expression and TILs. It’s very difficult in breast cancer to be PD-L1-positive and not having any tumor-infiltrating lymphocytes, but obviously it gives us a little bit more information than just TILs because it also tells us about the checkpoint status.
And so we are continuing to work on identifying the right patients, but at the moment it is in TNBC PD-L1-positive patients with whichever of the 2 established assays we are using. TMB is less relevant because it’s generally much lower compared to the other subtypes, but of course in those rare patients who have a high TMB immune therapy can be considered, and if they have TNBC they usually are also PD-L1-positive.
DR LOVE: Have you seen any MSI-high breast cancer?
PROF SCHMID: We do, but relatively infrequently, similar to the tumor mutational burden. It’s a small subgroup of patients, but they can be treated with immune checkpoint inhibitors per registered indication, but the experience with this in breast cancer is relatively limited at this point in time.
Professor Peter
Schmid, FRCP, MD, PhD
Featuring an interview with Prof Peter Schmid. Published August 2025.
Related links:
Home
Post-test
CE information and faculty disclosures
Select publications
PowerPoint slides
Download audio program
Companion video interview
Companion video lecture
Response to immunotherapy in breast cancer subtypes
DR LOVE: Welcome to “Oncology Today: Optimizing the Management of Metastatic BRCA-Negative, Triple-Negative Breast Cancer.” This is medical oncologist Dr Neil Love. For this program, I met with Prof Peter Schmid from Barts Cancer Institute in London. In addition to this interview, there is also a corresponding video program featuring Prof Schmid’s slide presentation.
To begin, I asked him to discuss the immunogenicity and potential response to checkpoint inhibitors that’s seen in breast cancer compared to other solid tumors.
PROF SCHMID: Yeah, a really important question. So breast cancer in general, and it’s always difficult to generalize, is less immunogenic compared to obviously melanoma but also lung cancer and some of the more squamous type diseases. But of course within breast cancer, such a wide and heterogeneous disease, there are some subgroups that have a high tumor mutational burden, high mutational load. Triple-negative breast cancer has probably the lowest-hanging fruit, but we equally see a group of patients with HER2-positive breast cancer who have a high mutational instability and therefore many neoantigens, and even in luminal B cancers in ER-positive breast cancer we probably have many tumor antigens and could consider that.
I would expect, and if you look at some of the data, the early studies, for example, in HER2-positive breast cancer, we saw actually interesting signals that were very similar to TNBC. We have seen in early ER-positive breast cancer, again in the neoadjuvant studies, a very powerful signal for the addition of immune therapy.
What is clear is the percentage of patients who may benefit from immune therapy is probably higher in TNBC compared to ER-positive breast cancer, but if you select the right patients, and we need to be more proactive in breast cancer compared to other tumor types to find the right patients who may benefit from immune therapy, and that group is small in ER-positive breast cancer, but still a group where I would expect immune therapy to work in the future.
At the moment PD-L1 seems to be, despite all the limitations, the best marker we have to select those patients. And PD-L1 in breast cancer is very different to for example lung cancer. In lung cancer, in a substantial proportion of patients, PD-L1 expression is found on cancer cells. In breast cancer most of the PD-L1 expression is actually on the immune infiltrate, and as such there’s a big overlap between PD-L1 expression and TILs. It’s very difficult in breast cancer to be PD-L1-positive and not having any tumor-infiltrating lymphocytes, but obviously it gives us a little bit more information than just TILs because it also tells us about the checkpoint status.
And so we are continuing to work on identifying the right patients, but at the moment it is in TNBC PD-L1-positive patients with whichever of the 2 established assays we are using. TMB is less relevant because it’s generally much lower compared to the other subtypes, but of course in those rare patients who have a high TMB immune therapy can be considered, and if they have TNBC they usually are also PD-L1-positive.
DR LOVE: Have you seen any MSI-high breast cancer?
PROF SCHMID: We do, but relatively infrequently, similar to the tumor mutational burden. It’s a small subgroup of patients, but they can be treated with immune checkpoint inhibitors per registered indication, but the experience with this in breast cancer is relatively limited at this point in time.
13
