Expert Robert L. Coleman, MD, details the final patient case and provides an overview of metastatic uterine serous carcinoma.
Robert L. Coleman, MD, FACOG, FACS: So now we're going to move on to our third case. This is a patient who has a uterine serous carcinoma, an unusual histology, but one that we're paying increasing attention to. So this is a 65-year-old postmenopausal woman, she presents with abnormal bleeding for 2 months. She has a history of uterine polyps. She has a BMI [body mass index] of 23 and her exam is notable for large uterus, and she's got some right lower quadrant tenderness on palpation. CA-125 [cancer antigen] is part of her work up. Probably the sequence here is that she had endometrial biopsy, it came back as high-grade, concerning for uterine serous, and then went on to a further work up. Her CA-125 was elevated and she ended up getting a PET-CT [positron emission tomography/computed tomography] that showed focal peritoneal nodules and then some equivale FDG-avid [fluorodeoxyglucose] lesions in the lung. Before we move on to her treatment, I'm curious, Krish, maybe we can start with you. Is part of a workup for an EMB [endomyocardial biopsy] that suggests that there might be serous neoplasm. I'm curious, first, what's your general workup? Is it similar to that? And secondly, what are your pathologists do with that tissue? Do they do any further annotation?
Krishnansu S. Tewari, MD: Yeah, so, if I have a serous biopsy, and usually these biopsies are coming from a lab outside of UCI [University of California Irvine] because they're done out in the community and the pathologist is never clear, they say serous-like features. So, I get the slides reviewed by our pathologist. If it is indeed a serous cancer at UCI, they can do [tumor protein] TP-53 on it. And so they'll do that. I typically order CT scans on them. In California. I can't get PET scans reimbursed or approved for endometrial cancer, so I'll definitely do a CT of the chest, abdomen, and pelvis before taking them to surgery. And as you know, half of these patients do present with gross upper abdominal disease and so it's very typical. Like this case, she needed a cytoreductive surgery. But there are some patients that I may give chemotherapy first, just like in a neoadjuvant setting, if I don't think I can cut all the disease out.
Robert L. Coleman, MD, FACOG, FACS: Yeah, no, that's a good point. So that's exactly what this patient had. She had a hysterectomy BSO [bilateral salpingo-oophorectomy] and a cytoreduction. And her final pathology basically came back as a uterine serous neoplasm with metastasis to peritoneal nodules. And her profile here you can see is ER negative [estrogen receptor], PR [progesterone receptor] negative, HER2 [human epidermal growth factor receptor 2], amplified with a TP-53 mutation. Michael, what do you think about that? Is that aligned with what your expectation would be with a serous cancer?
Michael J. Birrer, MD, PhD: Yeah, I think so. They could be ER and PR positive, but most of the time they have a lower frequency of expression of those hormone receptors. And quite frequently, very high frequency of TP-53 mutation, a lot like high-grade serous ovarian cancer. And then there's a subset of the HER2 amplified. And I'm assuming here, because it says amplified, that it's actually been done by FISH [fluorescence in situ hybridization], which is what I prefer. Because that means it's a driver, as opposed to just immunohistochemistry.
Robert L. Coleman, MD, FACOG, FACS: Histochemistry.
Michael J. Birrer, MD, PhD: Yeah. A lot of places will just do the latter. You could argue looking in the age of ADCs [antibody drug conjugates] to this doesn't really matter. I still think it's important to know that the gene is amplified.
Robert L. Coleman, MD, FACOG, FACS: Yeah, I think you're right. That's a really good call out. We don't have any approved drugs for IHC [immunohistochemistry], so expressing IHC, HER2, but in endometrial, in this particular high-grade neoplasm, we see HER2 expression north of 80% of these patients. The high level of expression and those associated with amplification is probably 20% to 25% of those cases, so it's much lower. But you're right. I think as this field evolves and we start thinking about additional potential therapies in HER2 low, just like we see in breast cancer. If that proves to be true, then you're right. We're going to have another renaissance of approaching this particular disease, which has been really tough in the past. So ultimately this patient has a FIGO [The International Federation of Gynecology and Obstetrics] stage IV-B uterine serous.
Michael J. Birrer, MD, PhD: I was just going to say the other point is, a lot of people think this is a rare tumor, being about 10% of endometrial cancer, but you know, the relapses and the recurrence and the death rate is much higher. It's at 40%.
Robert L. Coleman, MD, FACOG, FACS: Yeah, that's a good point.
Transcript edited for clarity.