High tumor infiltrating lymphocytes are significantly associated with pathological complete response in triple negative breast cancer treated with neoadjuvant KEYNOTE-522 chemoimmunotherapy.

INTRODUCTION: For patients with locally advanced triple negative breast cancer (TNBC), the standard of care is to administer the KEYNOTE-522 (K522) regimen, including chemotherapy and immunotherapy (pembrolizumab) given in the neoadjuvant setting. Pathological complete response (pCR) is more likely in patients who receive the K522 regimen than in patients who receive standard chemotherapy. Studies have shown that pCR is a strong predictor of long-term disease-free survival. However, factors predicting pCR to K522 are not well understood and require further study in real-world populations. METHODS: We evaluated 76 patients who were treated with the K522 regimen at our institution. Twenty-nine pre-treatment biopsy slides were available for pathology review. Nuclear grade, Nottingham histologic grade, Ki-67, lymphovascular invasion, and tumor infiltrating lymphocytes (TIL) were evaluated in these 29 cases. For the cases that did not have available slides for review from pre-treatment biopsies, these variables were retrieved from available pathology reports. In addition, clinical staging, race, and BMI at the time of biopsy were retrieved from all 76 patients' charts. Binary logistic regression models were used to correlate these variables with pCR. RESULTS: At the current time, 64 of 76 patients have undergone surgery at our institution following completion of K522 and 31 (48.4%) of these achieved pCR. In univariate analysis, only TIL was significantly associated with pCR (p = 0.014) and this finding was also confirmed in multivariate analysis, whereas other variables including age, race, nuclear grade, Nottingham grade, Ki-67, lymphovascular invasion, BMI, pre-treatment tumor size, and lymph node status were not associated with pCR (p > 0.1). CONCLUSION: Our real-world data demonstrates high TIL is significantly associated with pCR rate in the K522 regimen and may potentially serve as a biomarker to select optimal treatment. The pCR rate of 48.4% in our study is lower than that reported in K522, potentially due to the smaller size of our study; however, this may also indicate differences between real-world data and clinical trial results. Larger studies are warranted to further investigate the role of immune cells in TNBC response to K522 and other treatment regimens.

Prospective investigation of amino acid transport and PSMA-targeted positron emission tomography for metastatic lobular breast carcinoma.

PURPOSE: To explore the feasibility of imaging amino-acid transport and PSMA molecular pathways in the detection of metastatic breast invasive lobular carcinoma (ILC) and if there is superior detection compared to standard-of-care imaging [computed tomography (CT)/bone scan, or 18F-FDG positron-emission-tomography (PET)-CT]. METHODS: 20 women with de-novo or suspected metastatic ILC underwent two PET-CT scans with 18F-fluciclovine and 68Ga-PSMA-11 on separate days. Uptake per patient and in 3 regions per patient - ipsilateral axillary lymph node (LN), extra-axillary LN (ipsilateral supraclavicular or internal mammary), or distant sites of disease - was compared to standard-of-care imaging (CT/bone scan in 13 patients and 18F-FDG PET-CT in 7 patients). Results were correlated to a composite standard of truth. Confirmed detection rate (cDR) was compared using McNemar's test. Mean SUVmax of 18F-fluciclovine and 68Ga-PSMA-11 in the most avid lesion for each true positive metastatic region and intact primary lesion were compared by t-test. RESULTS: The cDR for standard-of-care imaging was 5/20 patients in 5/60 regions. 68Ga-PSMA-11 PET-CT detected metastasis in 7/20 patients in 7/60 regions. 18F-fluciclovine PET-CT detected metastasis in 9/20 patients in 12/60 regions. The cDR for 18F-fluciclovine PET-CT was significantly higher versus standard-of-care imaging on the patient and combined region levels, while there were no significant differences between 68Ga-PSMA-11 and standard-of care imaging. 18F-fluciclovine cDR was also significantly higher than 68Ga-PSMA-11 on the combined region level. Mean SUVmax for true positive metastatic and primary lesions with 18F-fluciclovine (n = 18) was significantly greater than for 68Ga-PSMA-11 (n = 11) [5.5 ± 1.8 versus 3.5 ± 2.7 respectively, p = 0.021]. CONCLUSION: In this exploratory trial, 18F-fluciclovine PET-CT has a significantly higher cDR for ILC metastases compared to standard-of-care imaging and to 68Ga-PSMA-11. Mean SUVmax for true positive malignancy was significantly higher with 18F-fluciclovine than for 68Ga-PSMA-11. Exploratory data from this trial suggests that molecular imaging of amino acid metabolism in patients with ILC deserves further study. CLINICAL TRIAL REGISTRATION: Early phase (I-II) clinical trial (NCT04750473) funded by the National Institutes of Health (R21CA256280).

Predicting outcomes in female germ cell tumors using a modified International Germ Cell Cancer Collaborative Group classification system to guide management.

OBJECTIVE: We previously developed preoperative and pre-chemotherapy modified versions of the male International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic model and assessed it in female patients with germ cell tumors (GCTs). We sought to validate these modified IGCCCG (mIGCCCG) models in a new cohort. METHODS: We queried institutional databases for female patients with GCTs treated at Memorial Sloan Kettering Cancer Center from 1/1/1990-6/1/2020. The mIGCCCG model classifies patients with non-dysgerminomas as good, intermediate, or poor risk based on tumor markers using male IGCCCG cutoffs and absence/presence of non-pulmonary/peritoneal visceral metastasis. In dysgerminomas, good- and intermediate-risk groups are defined by absence/presence of non-pulmonary/peritoneal visceral metastasis. Progression-free survival (PFS) and overall survival (OS) were estimated for each group in the validation and combined original and validation cohorts. Associations between individual clinical factors and outcomes were evaluated. RESULTS: Among 183 female patients with GCTs, clinical characteristics and outcomes were similar between the original (n = 93) and validation (n = 90) cohorts. In multivariable models, higher stage, older age, and non-dysgerminoma histology predicted worse PFS and OS (p < 0.05). Among 162 patients who received chemotherapy, preoperative and pre-chemotherapy mIGCCCG models were significantly associated with PFS and OS (p < 0.001 for all groups). With the preoperative model, 3-year PFS rates were 94%, 76%, and 50% in the good-, intermediate-, and poor-risk patients, respectively; OS rates were 96%, 86%, and 52%, respectively. Even within stage groups, mIGCCCG risk classifications were associated with clinical outcomes. CONCLUSIONS: A female-specific mIGCCCG risk model effectively stratifies patients and should be incorporated into clinical trials.

Percutaneous CT-Guided Cryoneurolysis of the Intercostobrachial Nerve for Management of Postmastectomy Pain Syndrome.

PURPOSE: To evaluate the feasibility, safety, and efficacy of intercostobrachial nerve (ICBN) cryoneurolysis for pain control in patients with postmastectomy pain syndrome (PMPS). MATERIALS AND METHODS: Fourteen patients with PMPS were prospectively enrolled into this clinical trial after a positive response to a diagnostic computed tomography (CT)-guided percutaneous block of the ICBN. Participants subsequently underwent CT-guided percutaneous cryoneurolysis of the same nerve and were observed on postprocedural Days 10, 90, and 180. Pain scores, quality-of-life measurements, and global impression of change values were recorded before the procedure and at each follow-up point using established validated outcome instruments. RESULTS: Cryoneurolysis of the ICBN was technically successful in all 14 patients. The mean pain decreased significantly by 2.1 points at 10 days (P = .0451), by 2.4 points at 90 days (P = .0084), and by 2.9 points at 180 days (P = .0028) after cryoneurolysis. Pain interference with daily activities decreased significantly by 14.4 points after 10 days (P = .0161), by 16.2 points after 90 days (P = .0071), and by 20.7 points after 180 days (P = .0007). There were no procedure-related adverse events. CONCLUSIONS: Cryoneurolysis of the ICBN in patients with PMPS was technically feasible and safe and resulted in a significant decrease in postmastectomy pain for up to 6 months in this small cohort.

Improving palbociclib adherence among women with metastatic breast cancer using a CONnected CUstomized Treatment Platform: A pilot study.

OBJECTIVE: To pilot test a mobile health intervention using a CONnected CUstomized Treatment Platform that integrates a connected electronic adherence monitoring smartbox and an early warning system of non-adherence with bidirectional automated texting feature and provider alerts. METHODS: In total, 29 adult women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer and a prescription for palbociclib were asked to complete a survey and participate in a CONnected CUstomized Treatment Platform intervention, including use of a smartbox for real-time adherence monitoring, which triggered text message reminders for any missed or extra dose, and referrals to (a) participant's oncology provider after three missed doses or an episode of over-adherence, or (b) a financial navigation program for any cost-related missed dose. Use of smartbox, number of referrals, palbociclib adherence, CONnected CUstomized Treatment Platform usability measured by System Usability Scale, and changes in symptom burden and quality of life were assessed. RESULTS: Mean age was 57.6 and 69% were white. The smartbox was used by 72.4% of participants, with palbociclib adherence rate of 95.8%±7.6%. One participant was referred to oncology provider due to missed doses and one was referred to financial navigation. At baseline, 33.3% reported at least one adherence barrier including inconvenience to get prescription filled, forgetfulness, cost, and side effects. There were no changes in self-reported adherence, symptom burden or quality of life over 3 months. CONnected CUstomized Treatment Platform usability score was 61.9 ± 14.2. CONCLUSION: The CONnected CUstomized Treatment Platform interventions is feasible, resulting in a high palbociclib adherence rate without any decline in overtime. Future efforts should focus on improving usability.

Utility of Oncotype DX score in clinical management for T1 estrogen receptor positive, HER2 negative, and lymph node negative breast cancer.

BACKGROUND: The management of estrogen receptor positive (ER+)/HER2- and lymph node (LN) negative breast cancers can be influenced by Oncotype DX recurrence score (RS) in the USA. However, the benefit of RS in T1 tumors (≤ 1 cm) is not clear. METHODS: We retrieved 199 T1 ER+/HER2-/LN- breast cancer diagnosed between 1993 and 2016 that had undergone RS testing. The median follow-up time was 51 months. We examined the disease-free survival (DFS) and distant metastasis and their association with RS and other clinicopathologic features. RESULTS: Of the 199 cases, 40 were T1a (≤ 0.5 cm) and 159 were T1b (> 0.5 cm to 1 cm) tumors. In the 40 T1a tumors, 11 would benefit from chemotherapy by the TAILORx study results. Of these T1a tumors, 36 were Nottingham grade 1/2, 3 were grade 3, and 1 was microinvasive carcinoma; 2 (5%) had local recurrence and 1 (2.5%) had distant metastasis to the bone. The only patient with T1a tumor (Nottingham grade 3, RS = 42) and distant metastasis to bone had received adjuvant chemotherapy. In the 159 T1b tumors, 25 would benefit chemotherapy by the TAILORx results. Of the T1b tumors, 149 were Nottingham grade 1/2 and 10 were grade 3. Nine (5.7%) had local recurrence and 2 (1.3%) had distant metastasis to bone and mediastinum, respectively. The two T1b tumors with distant metastasis had a RS 20 and Nottingham grade 2, and RS 27 and Nottingham grade 3, respectively. Both patients received adjuvant chemotherapy. In multivariate analysis of the entire cohort (T1a and T1b tumors), Nottingham tumor grade and receiving chemotherapy were significantly associated with DFS. In univariate analysis of the entire cohort, Nottingham tumor grade, receiving adjuvant chemotherapy, and RS were significantly associated with distant metastasis. CONCLUSION: This study demonstrates that the metastatic rate of T1a and T1b ER+/HER2-/LN- breast cancer is very low. Patients with low grade (1 or 2), T1a ER+/HER2-/LN- breast cancer may not need RS for treatment decision-making; however, in patients with high-grade T1a or T1b ER+/HER2-/LN- breast cancer, RS analysis should be strongly considered.

Optimizing the Duration of Trastuzumab: A Fresh Perspective.

Prior to the introduction of trastuzumab, the first targeted anti-HER2 agent, in 1998, patients diagnosed with HER2-positive breast cancer felt like they were being handed a death sentence. Despite treatment with aggressive chemotherapy, their tumors recurred faster, more often spread to brain and liver, and were associated with higher rates of death than HER2-negative tumors. HER2-positive breast cancer was also more prevalent in younger patients, making the diagnosis even more devastating. However, in the 1980s, cancer researcher Axel Ullrich, PhD, and oncologist Dennis Slamon, MD, PhD, recognized that HER2 could be targeted by a small molecule that binds to the receptor on the cell surface and blocks the signal telling the cell to divide. This small molecule was called trastuzumab, and it eventually completely changed how HER2-positive breast cancer was treated.

The Impact of Genetic Counseling Educational Tools on Patients' Knowledge of Molecular Testing Terminology.

Molecular testing is increasingly being integrated into cancer management. Despite rapid advancements, little work has been done to explore strategies for communicating with patients undergoing molecular tumor testing. This study evaluated the impact of genetic counseling educational tools on improving patients' understanding of key terms related to molecular testing. A genetic counseling intern designed a picture book to explain six words found in prior research to be difficult to understand (mutation, germline mutation, somatic mutation, biomarker, molecular testing, and targeted therapy). Participants who had previously discussed molecular testing with their oncologist were asked to define the terms. The same participants then received an explanation of each term either from the intern using the picture book in person or from a video presentation of the picture book. They were then asked to redefine each term afterward. The difference between the number of terms defined correctly pre- and post-intervention was compared between presentations. Sixty-three patients with melanoma, colon, lung, or breast cancer were recruited. After both interventions, correct understanding rates improved for all six terms, with significant improvement for germline mutation (p < 0.001), somatic mutation (p < 0.001), biomarker (p < 0.001), and molecular testing (p < 0.001). Understanding of targeted therapy improved significantly (p = 0.011) for the video presentation only. Mean change in knowledge scores did not differ between the two interventions (intern presentation 3.2 vs. video 2.9, p = 0.428). Our data suggest that genetic counseling educational tools can increase patient understanding of terms used to describe molecular testing.

A randomized, controlled phase II trial of neoadjuvant ado-trastuzumab emtansine, lapatinib, and nab-paclitaxel versus trastuzumab, pertuzumab, and paclitaxel in HER2-positive breast cancer (TEAL study).

BACKGROUND: Neoadjuvant dual human epidermal growth factor receptor (HER2) blockade with trastuzumab and pertuzumab plus paclitaxel leads to an overall pathologic complete response (pCR) rate of 46%. Dual HER2 blockade with ado-trastuzumab emtansine (T-DM1) and lapatinib plus nab-paclitaxel has shown efficacy in patients with metastatic HER2-positive breast cancer. To test neoadjuvant effectiveness of this regimen, an open-label, multicenter, randomized, phase II trial was conducted comparing T-DM1, lapatinib, and nab-paclitaxel with trastuzumab, pertuzumab, and paclitaxel in patients with early-stage HER2-positive breast cancer. METHODS: Stratification by estrogen receptor (ER) status occurred prior to randomization. Patients in the experimental arm received 6 weeks of targeted therapies (T-DM1 and lapatinib) followed by T-DM1 every 3 weeks, lapatinib daily, and nab-paclitaxel weekly for 12 weeks. In the standard arm, patients received 6 weeks of trastuzumab and pertuzumab followed by trastuzumab weekly, pertuzumab every 3 weeks, and paclitaxel weekly for 12 weeks. The primary objective was to evaluate the proportion of patients with residual cancer burden (RCB) 0 or I. Key secondary objectives included pCR rate, safety, and change in tumor size at 6 weeks. Hypothesis-generating correlative assessments were also performed. RESULTS: The 30 evaluable patients were well-balanced in patient and tumor characteristics. The proportion of patients with RCB 0 or I was higher in the experimental arm (100% vs. 62.5% in the standard arm, p = 0.0035). In the ER-positive subset, all patients in the experimental arm achieved RCB 0-I versus 25% in the standard arm (p = 0.0035). Adverse events were similar between the two arms. CONCLUSION: In early-stage HER2-positive breast cancer, the neoadjuvant treatment with T-DM1, lapatinib, and nab-paclitaxel was more effective than the standard treatment, particularly in the ER-positive cohort. TRIAL REGISTRATION: Clinicaltrials.gov NCT02073487 , February 27, 2014.

Breast Cancer and Heart Failure.

Heart failure and breast cancer have shared risks and morbidities. Multimodality therapies for breast cancer, including conventional chemotherapy, targeted therapeutics, radiation therapy, and hormonal agents, may make patients more susceptible to asymptomatic left ventricular dysfunction and clinical heart failure during and after treatment. New or preexisting left ventricular dysfunction may lead to interruptions in cancer treatment and limit options of breast cancer systemic therapy, leading to adverse outcomes. Early recognition and management of cardiovascular risk factors before, during, and after cancer treatment are of utmost importance. This review presents advances, challenges, and opportunities for cardiovascular care in contemporary breast cancer treatment.

Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer.

PURPOSE: The current American Joint Committee on Cancer (AJCC) staging manual uses tumor size, lymph node, and metastatic status to stage breast cancer across different subtypes. We examined the prognosis of triple-negative breast cancer (TNBC) versus non-TNBC within the same stages and sub-stages to evaluate whether TNBC had worse prognosis than non-TNBC. METHODS: We reviewed the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) data and identified 158,358 patients diagnosed with breast cancer from 2010 to 2012. The overall survival (OS) time and breast cancer cause-specific survival time were compared between patients with TNBC and non-TNBC in each stage and sub-stages. The results were validated using a dataset of 2049 patients with longer follow-up from our institution. RESULTS: Compared with patients with non-TNBC, patients with TNBC had worse OS and breast cancer cause-specific survival time in every stage and sub-stage in univariate and multivariate analyses adjusting for age, race, tumor grade, and surgery and radiation treatments in the SEER data. The worse OS time in patients with TNBC was validated in our institutional dataset. CONCLUSIONS: Patients with TNBC have worse survival than patients with non-TNBC. The new AJCC staging manual should consider breast cancer biomarker information.

Prevention and Screening in Hereditary Breast and Ovarian Cancer.

In recent years, we have learned a great deal about pathogenic mutations that increase the risk of breast and ovarian cancer, particularly mutations in the BRCA1 and BRCA2 genes. Here we review current guidelines on breast and ovarian cancer screening, prophylactic surgery, and other risk-reduction strategies in patients with these mutations, and we detail the data that drive these recommendations. We also discuss guidelines on screening and management for other cancers associated with BRCA1 and BRCA2, such as male breast cancer, pancreatic cancer, and prostate cancer. Discussions about genetic testing have become more complex with the advent of panel testing, which often allows for testing of a more comprehensive panel of genes than traditional BRCA1 and BRCA2 testing, but which is also associated with a higher likelihood of obtaining results with less clear data to inform management. It is difficult to come to a consensus on how best to address the varied and potentially challenging situations that may arise from genetic testing. The complexity inherent in managing these cases makes a multidisciplinary team-including medical oncologists, surgical oncologists, genetic counselors, reproductive endocrinologists, and medical ethicists-critical to optimization of care.

The role of systemic chemotherapy in the management of granulosa cell tumors.

OBJECTIVE: Granulosa cell tumors (GCTs) are rare, and the role of chemotherapy in their management is not clearly defined. METHODS: We performed a retrospective cohort study of GCT patients diagnosed from January 1996 through June 2013 at the Memorial Sloan Kettering Cancer Center, comparing those who received adjuvant chemotherapy to those who did not. Differences between groups were assessed using the log-rank test. Statistical significance was set at p<0.05. RESULTS: Of 118 patients, 10 (8%) received adjuvant chemotherapy (1 [1%] of 103 stage I and 9 [60%] of 15 stage II-IV patients). Thirty-two patients (27%) experienced disease recurrence. Four patients had residual disease after initial surgery, and all received adjuvant chemotherapy; each recurred within 24.3 months (median PFS, 8.2 months). The time to first recurrence was longer in patients who did not receive adjuvant chemotherapy. For patients with recurrent disease, receiving chemotherapy after surgery for first recurrence did not seem to improve time to second recurrence versus surgery alone (HR 0.98; p=0.965). Additionally, 12 patients (10%) had a previous diagnosis of breast cancer-an incidence rate 3.22 times higher than Surveillance, Epidemiology, and End Results (SEER) data predicts (p<0.001). CONCLUSIONS: Although the numbers were small, in this analysis chemotherapy was not found to improve the recurrence-free interval of patients with GCTs, a finding that requires prospective validation. Residual disease after surgery was associated with poor prognosis. Finally, there was a significantly higher than expected incidence of antecedent breast cancer in this population, an association that deserves further exploration.

Development of a risk stratification system to guide treatment for female germ cell tumors.

OBJECTIVE: Due to their rarity, little is known about prognostic factors in female germ cell tumors (GCTs) or outcomes following systemic therapy. Management is largely based on studies of male GCT and epithelial ovarian cancer. METHODS: Chart review was performed for all females with GCT seen at Memorial Sloan Kettering Cancer Center (MSKCC) from 1990 to 2012. Patients receiving chemotherapy were stratified using a modification of the male IGCCCG risk system, and the classifier was correlated with outcome. RESULTS: Of 93 patients, 92 (99%) underwent primary surgery and 85 (92%) received chemotherapy. Modified IGCCCG classification was significantly associated with progression-free survival (PFS) and overall survival (OS), both when applied preoperatively and pre-chemotherapy (p<0.001 for all four analyses). Progression after initial chemotherapy (n=29) was detected by imaging in 14 (48%) patients, by serum tumor markers in 6 (21%) patients, and by multiple methods in the rest. Seven (29%) of 24 patients treated with salvage chemotherapy achieved long-term PFS, including 4/6 who received high-dose chemotherapy (HDCT) as initial salvage versus 3/16 treated with other initial salvage regimens. The estimated 3-year OS rate was 84% (95% CI, 76-92%), with a trend favoring dysgerminoma over non-dysgerminoma histologies (p=0.12). CONCLUSIONS: Modified IGCCCG classification was prognostic for female GCT patients in this cohort and identified a poor-risk group who may benefit from more intensive first-line chemotherapy. Both imaging and tumor marker evaluation were important in identifying relapses after first-line chemotherapy. The majority of long-term remissions with salvage therapy were achieved with initial salvage HDCT.

Sentinel lymph node biopsy in pregnant women with breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SNB) in pregnant women with breast cancer is uncommonly pursued given concern for fetal harm. This study evaluated efficacy and safety outcomes in pregnant breast cancer patients undergoing SNB. METHODS: Patients who underwent SNB while pregnant were identified from a retrospective parent cohort of women diagnosed with breast cancer during pregnancy. Chart review was performed to tabulate patient/tumor characteristics, method/outcome of SNB, and short-term maternal/fetal outcomes. RESULTS: Within a cohort of 81, 47 clinically node-negative patients had surgery while pregnant: 25 (53.2 %) SNB, 20 (42.6 %) upfront axillary lymph node dissection, and 2 (4.3 %) no lymph node surgery. Of SNB patients, 8, 9, and 8 had SNB in the first, second, and third trimesters, respectively. 99 m-Technetium (99-Tc) alone was used in 16 patients, methylene blue dye alone in 7 patients, and 2 patients had unknown mapping method. Mapping was successful in all patients. There were no SNB-associated complications. At a median of 2.5 years from diagnosis, there was one locoregional recurrence, one new primary contralateral tumor, three distant recurrences, and one breast cancer death. Among patients who underwent SNB, there were 25 liveborn infants, of whom 24 were healthy, and 1 had cleft palate (in the setting of other maternal risk factors). CONCLUSIONS: SNB in pregnant breast cancer patients appears to be safe and accurate using either methylene blue or 99-Tc. This is one of the largest reported experiences of SNB during pregnancy; however, numbers remain limited. SNB rates in this cohort were lower than in non-pregnant breast cancer patients.

Datopotamab-deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.

Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes. Here we tested datopotamab-deruxtecan (Dato-DXd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin-cyclophosphamide (block C). Patients are randomized into arms consisting of different investigational block A treatments. Algorithms based on magnetic resonance imaging and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathological complete response, the primary endpoint. There are two primary efficacy analyses: after block A and across all blocks for the six prespecified breast cancer subtypes (defined by clinical hormone receptor/human epidermal growth factor receptor 2 (HER2) status and/or the response-predictive subtypes). We report results of 103 patients treated with Dato-DXd. While Dato-DXd did not meet the prespecified threshold for success (graduation) after block A in any subtype, the treatment strategy across all blocks graduated in the hormone receptor-negative HER2-Immune-DNA repair deficiency- subtype with an estimated pathological complete response rate of 41%. No new toxicities were observed, with stomatitis and ocular events occurring at low grades. Dato-DXd was particularly active in the hormone receptor-negative/HER2-Immune-DNA repair deficiency- signature, warranting further investigation, and was safe in other subtypes in patients who followed the treatment strategy. ClinicalTrials.gov registration: NCT01042379 .

Recurrent uterine inflammatory myofibroblastic tumor previously managed as leiomyosarcoma has sustained response to alectinib.

Soft tissue sarcomas encompass a wide range of histologic subtypes with varied clinical implications. The incorporation of comprehensive genetic profiling into clinical practice is refining our ability to make these distinctions in diagnosis to better reflect prognosis and clinical behavior of a tumor. In this report, we describe a case of recurrent inflammatory myofibroblastic tumor (IMT) of the uterus, initially diagnosed and managed as leiomyosarcoma. At the time of recurrence, the patient was found to have a TNS1-ALK rearrangement and was treated successfully with alectinib, a second-generation anaplastic lymphoma kinase (ALK)-inhibitor. She had a complete response by imaging six months after initiation of alectinib and remains without evidence of disease at 36 months follow-up. Pathology review in the setting of her known ALK fusion and the 2020 update to the World Health Organization Classification of Female Genital Tumors led to a change in diagnosis from leiomyosarcoma to IMT. Our case highlights the role of molecular testing in the diagnosis and management of uterine mesenchymal tumors and the efficacy of alectinib in this ALK-rearranged recurrent IMT of the uterus. Care must be taken to differentiate between IMT and other uterine mesenchymal tumors as this distinction can impact prognosis and management. Furthermore, this case adds to the growing body of evidence supporting the paradigm shift toward developing molecularly targeted therapies rather than disease site-specific treatments, especially in cases of recurrence as recommended by the National Comprehensive Cancer Network.

Case report of lymph node activation mimicking cancer progression: A false positive F18 FDG PET CT after COVID-19 vaccination.

This case illustrates a false positive F18 FDG PET CT in the left axilla of a woman being treated for metastatic breast cancer after COVID-19 vaccination. Follow-up ultrasound of the axilla indicated no metastasis, indicating that the lymphadenopathy was likely due to an immune response following vaccination. This case report, in conjunction with prior studies of other vaccines with similar findings suggest that providers should be aware of potential false positive imaging following COVID-19 vaccination. In light of these findings, clinicians and imaging providers should record the date and side of the vaccination and inform patient of potential false positive results to reduce patient anxiety and unnecessary tests as COVID-19 vaccines become widely available.

Clinicopathologic Factors Associated With Response to Neoadjuvant Anti-HER2-Directed Chemotherapy in HER2-Positive Breast Cancer.

BACKGROUND: HER2-targeted neoadjuvant therapy has high efficacy in treating HER2-positive breast cancer. Response to neoadjuvant therapy helps clinicians make treatment decisions and make estimates about prognosis. This study examined clinicopathologic features to determine which may be most predictive of response to neoadjuvant therapy in HER2+ breast cancer. PATIENTS AND METHODS: Patients with HER2+ breast cancer (n = 173) who had an initial biopsy performed between 2010 and 2016 were identified at our institution. Tumor response was evaluated on excisional specimens using the MD Anderson residual cancer burden (RCB) classification. Tumors with pathologic complete response (defined as no residual invasive carcinoma in the breast and lymph nodes) and RCB-I were classified as having response and tumors with RCB-II and -III as having no response. Patient age, tumor size, nuclear grade (1/2 vs. 3), mitosis, Nottingham grade, HER2 immunohistochemistry (1/2+ vs. 3+), HER2/CEP17 (chromosome enumeration probe 17) ratio, HER2 copy number, estrogen receptor, progesterone receptor, Ki-67, and tumor-infiltrating lymphocytes (TIL) were evaluated and correlated with response. TILs were evaluated for an average and also for the hot spot/total tumor stromal ratio. RESULTS: Small tumor size, low estrogen receptor and progesterone receptor expression, HER2 immunohistochemistry 3+, high Ki-67, high HER2/CEP17 ratio, and high HER2 copy number were significantly associated with response (all P < .05). TIL hot spot was associated with RCB in univariate (P < .05) but not multivariate analyses. CONCLUSION: Clinicopathologic features may help predict HER2+ breast cancer response to neoadjuvant therapy. Larger studies would be useful to confirm these associations, which may have relevance to clinical practice.