Shortly before I was elected President of ASCO, I attended the 65th birthday party of a current patient. She had been diagnosed 10 years earlier with metastatic breast cancer and hadn't been sure she wanted to move forward with further treatment. With encouragement, she elected to participate in a clinical trial of an investigational drug that is now widely used to treat breast cancer. Happily, here we were, celebrating with her now-married daughters, their husbands, and three beautiful grandchildren, ages 2, 4, and 8. Such is the importance of clinical trials and promising new therapies.Clinical research is about saving and improving the lives of individuals with cancer. It's a continuing story that builds on the efforts of untold numbers of researchers, clinicians, caregivers, and patients. ASCO's Clinical Cancer Advances report tells part of this story, sharing the most transformative research of the past year. The report also includes our latest thinking on the most urgent research priorities in oncology.ASCO's 2020 Advance of the Year-Refinement of Surgical Treatment of Cancer-highlights how progress drives more progress. Surgery has played a fundamental role in cancer treatment. It was the only treatment available for many cancers until the advent of radiation and chemotherapy. The explosion in systemic therapies since then has resulted in significant changes to when and how surgery is performed to treat cancer. In this report, we explore how treatment successes have led to less invasive approaches for advanced melanoma, reduced the need for surgery in renal cell carcinoma, and increased the number of patients with pancreatic cancer who can undergo surgery.Many research advances are made possible by federal funding. With the number of new US cancer cases set to rise by roughly a third over the next decade, continued investment in research at the national level is crucial to continuing critical progress in the prevention, screening, diagnosis, and treatment of cancer.While clinical research has translated to longer survival and better quality of life for many patients with cancer, we can't rest on our laurels. With ASCO's Research Priorities to Accelerate Progress Against Cancer, introduced last year and updated this year, we've identified the critical gaps in cancer prevention and care that we believe to be most pressing. These priorities are intended to guide the direction of research and speed progress.Of course, the effectiveness or number of new treatments is meaningless if patients don't have access to them. High-quality cancer care, including clinical trials, is out of reach for too many patients. Creating an infrastructure to support patients is a critical part of the equation, as is creating connections between clinical practices and research programs. We have much work to do before everyone with cancer has equal access to the best treatments and the opportunity to participate in research. I know that ASCO and the cancer community are up for this challenge.Sincerely,Howard A. "Skip" Burris III, MD, FACP, FASCOASCO President, 2019-2020.
Abstract T-DXd has been approved by the FDA to treat patients with metastatic HER2-low and -positive breast cancer. The utility of current HER2 immunohistochemistry (IHC) assays in evaluating HER2-low tumors is not clear. A simple and objective method to evaluate HER2 expression in breast cancer is urgently needed. RNAScope can detect HER2 RNA levels by in situ hybridization using one regular unstained FFPE slide and processed using the Leica BOND-III autostainer that is readily available in many clinical laboratories. RNA level detected by RNAScope can be quantified by dots/cell using publicly available software. Therefore, RNAScope is a practical assay and could be a promising alternative to IHC to quantify HER2 levels in breast cancer. We evaluated HER2 levels in 605 breast cancer tissue microarray cores using RNAScope and the two most commonly used FDA approved HER2 IHC assays: Ventana PATHWAY (PATHWAY) and Dako HercepTest (HercepTest). Clinical data were available for 505 cores from 347 patients. RNA level (dots/cell) by RNAScope was quantified using publicly available software QuPath. IHC assays were scored as 0, ultralow (UL, >0% but ≤10% incomplete membranous staining), 1+, 2+ and 3+. In addition, HER2 protein levels (AQUA protein level) were quantified from 100 cores through regression analysis, using AQUA score against cell line arrays with pre-calibrated HER2 protein levels determined by mass spectrometry. We used ANOVA to assess the differences in RNAScope results among the five IHC scores, and linear regressions to correlate RNAScope with HER2 AQUA protein levels. We finally evaluated 41 RNAScope whole-slide images (IHC 1+: n=5; 2+: n=26; 3+: n=10) of metastatic tumors from 31 patients treated with T-DXd. No significant differences of RNAScope results were observed among the 0, UL, and 1+ cores in both IHC assays, indicating the current IHC assays cannot differentiate HER levels in HER2-low tumors. However, statistically significant differences (p < 0.0001) were found among the IHC 1+, 2+, and 3+ cores and higher RNAScope dots/cell was associated with higher stage of the tumors. There was a strong correlation (R2 = 0.610) between the RNAScope results and quantitative HER2 AQUA protein level in the 100 cores. There were significantly higher HER2 RNA levels in the 41 metastatic biopsies with higher IHC scores (p < 0.05). When we used RNAScope to measures HER2 levels in metastases right before T-DXd treatment, there was numerically (p=0.881) higher HER2 RNA levels in responders (5.60±8.82 dots/cell) vs non-responders (5.20±5.31). Interestingly, the HER2 RNA levels in bone metastases was statistically higher (p=0.030) in non-responders (5.24±2.87, n=3) than in responders (1.55±0.81, n=5); although number of patients was low. For the non-bone metastases (esophagus, lymph node, liver, brain, lung), HER2 RNAScope values were numerically higher (p=0.261) in responders (9.65±2.87, n=5) than non-responders (5.19±5.74, n=15). In these non-bone metastatic cases, the response rates by IHC scores were 100% in 1+ cases, 24% in 2+ and 33% in 3+. When we used AI assisted categories based on RNAScope results, the response rates were 20% in RNAScope 1+ cases, 20% in 2+, 50% in 3+ cases. Our study shows that current IHC assays are unable to differentiate HER2 levels between IHC 0 and 1+ breast cancer cases, which is a critical issue in properly identifying patients who will benefit from T-DXd treatment. RNAScope results strongly correlate with HER2 protein levels and showed similar RNA levels among IHC 0 and 1+ cases. RNAScope is a simple and objective assay to quantify HER2 levels by dots/cell using publicly available software and may help better identify which patients benefit from T-DXd treatment. Other factors besides HER2 level may also contribute to the response rate in patients treated with T-DXd. RNAScope results in association with immunohistochemistry (IHC) scores by PATHWAY, HercepTest, and in biopsies from patients treated with T-DXd (T-DXd cohort). XX XX No significant (ns) difference of RNAScope dots/cell were seen among 0, UL and 1+ cases by both PATHWAY and HercepTest assays. There were significant differences of dots/cell comparing 1+, 2+ and 3+ cases. Note: ns not significant (p>0.05), * p<0.05, *** p<0.001, **** p<0.0001 Citation Format: Xiaoxian Li, Ji-Hoon Lee, Yuan Gao, Jilun Zhang, Katherine Bates, David Rimm, Huina Zhang, Geoffrey Smith, Diane Lawson, Jane Meisel, Jenny Chang, Lei Huo. RNAScope: a practical approach and promising alternative to immunohistochemistry to quantify HER2 expression in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-13-03.
1117 Background: SNB in PABC is not often pursued due to concerns for potential fetal harm. There are only limited data available regarding the safety and efficacy of SNB in patients (pts) with PABC. Methods: Pts with PABC who underwent SNB were identified from within an existing multi-institutional PABC cohort diagnosed 1996-2013. Factors evaluated included method and result of SNB evaluation, maternal disease outcome, and fetal outcomes. Results: Within a cohort of 78 PABC pts, 53 had breast surgery while pregnant; 23 (43%) underwent SNB, 27 (51%) underwent initial axillary node (AN) dissection, 18 of whom were clinically node negative, and 3 had no nodal evaluation. Of SNB pts, 21 (91%) had stage 1-2 disease; 14 (61%) had ER/PR+ disease and 7 (30%) HER2+. Eight (35%), 9 (39%), and 6 (26%) women had SNB in the first, second, and third trimesters, respectively. 99-Technetium-labelled sulfur colloid (99-Tc) alone was used for SNB in 14 pts; methylene blue (MB) dye alone was used in 7. SN was identified in 100% of pts; see Table. There were no SNB-associated complications. At a median of 2.4 years from diagnosis, there were no locoregional recurrences, 3 (13%) distant recurrences, and 1 (4%) death from breast cancer. Among pts who underwent SNB, there were 20 liveborn infants and 3 pregnancies ongoing. Of the 20 infants born, 18 were healthy, 1 unknown, and 1 had cleft palate (in setting of maternal risk factors including smoking and methadone). Conclusions: SNB in PABC appears to be a safe and accurate procedure using either 99-Tc or MB techniques. This is one of the largest experiences reported to date of SNB during PABC; however, numbers remain limited and rates of SNB in our cohort were lower than current rates in non-PABC patients. Additional research and monitoring for safety of this procedure is warranted in women with PABC. [Table: see text]
e17549 Background: Ovarian cancer is the most lethal gynecologic cancer with roughly 20% of cases attributable to mutations in BRCA 1 or BRCA 2. In 2018, the SOLO-1 study, comparing PARPi to placebo in BRCA 1/2 mutated ovarian cancers following first-line chemotherapy showed an unprecedented 70% reduction in the hazard to progression or death. Consequently, in 2020, ASCO published a consensus statement recommending germline testing for all women with epithelial ovarian cancer. Currently, our understanding of the improvement, or lack thereof, in germline testing for ovarian cancers following these changes are not well described, and research is needed to determine the real-world frequency of and barriers to genetic testing. Methods: We retrospectively reviewed 115 patients’ charts with newly diagnosed ovarian cancer from 2012-2022 at Grady Memorial Hospital. An assessment of genetic testing was acquired, including genetic counseling referral frequency, attrition, somatic tumor testing, and mutated genes identified. Additional characteristics including age, race, histology, grade, and stage were obtained. Univariate association (Chi-square or Fisher’s exact test) was performed to correlate the above variables with germline testing. Results: Of 115 patients diagnosed with ovarian cancer from 2012–2022, 33% received a genetic counseling referral and 16.5% received an evaluation. Germline testing, in lieu of referral, was ordered by the physician in 20% of cases. Among patients who completed germline testing, a pathogenic mutation was found in 9.8% of patients. Patients who were ≤ 48 years old were more likely to be referred for genetic counseling (50% vs. 26.5%, p = 0.016), and those with earlier stage disease (stage 1 or 2 versus stage 3 or 4) were more likely to be referred for genetic counseling (46.5% vs. 25%, p = 0.018). There was a significant difference in those receiving genetic counseling referral pre and post October 2018 (when SOLO-1 was published) with 50% of patients being referred after October 2018 versus 18% of patient before referred prior (p = 0.005), and in 2021 (following the ASCO consensus statement), an impressive 63.6% of patients were referred with attrition rate of 54.5%. Conclusions: Our real-world data demonstrates improvement in germline testing for newly diagnosed ovarian cancers at our institution over the past decade, with significant increases in both genetic counseling referral and attrition since 2018. Despite these improvements, we continue to be deficient in testing patients who are older and with more advanced-stage disease, which may be due to the gravity of their presentation and prioritized focus of treatment initiation. System-wide changes, including the option of having genetic testing ordered by the oncologist in the clinic with genetic counseling performed after results are available, are being explored.
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