A 41-year-old woman with invasive lobular carcinoma of the breast underwent sequential 68Ga-PSMA-11 PET/CT and 18F-fluciclovine PET/CT as part of an ongoing clinical trial (NCT04750473). 68Ga-PSMA PET/CT showed increased radiotracer uptake in the uterine endometrium and left adnexa. 18F-fluciclovine PET/CT showed increased radiotracer uptake in a leiomyomatous uterus. A clinical 18F-FDG PET/CT demonstrated radiotracer uptake in the endometrium and a circumferential area of uptake in the left adnexa, a pattern more similar to the 68Ga-PSMA uptake pattern. This case highlights the discordance in the uptake pattern of 2 radiotracers approved for prostate cancer imaging but increasingly used in non-prostate malignancies imaging.

Background: Two large randomized trials, CALGB 9343 and PRIME II, support omission of radiotherapy after breast conserving surgery (BCS) in elderly women with favorable-risk early stage breast cancer intending to take endocrine therapy. However, patients with grade 3 histology were underrepresented on these trials. We hypothesized that high-grade disease may be unsuitable for treatment de-escalation and report the oncologic outcomes for elderly women with favorable early stage breast cancer treated with BCS with or without radiotherapy. Materials and Methods: The Surveillance, Epidemiology, and End Results database was queried for women between 70 and 79 years of age with invasive ductal carcinoma diagnosed between 1998 and 2007. This cohort was narrowed to women with T1mic-T1c, N0, estrogen receptor-positive, invasive ductal carcinoma treated with BCS with or without external beam radiation (EBRT). The primary endpoints were 5- and 10-year cause-specific survival (CSS). Univariate and multivariate analyses were performed. Propensity-score matching of T-stage, year of diagnosis, and age was utilized to reduce selection bias while comparing treatment arms within the grade 3 subgroup. Results: A total of 12,036 women met inclusion criteria, and the median follow-up was 9.4 years. EBRT was omitted in 22% of patients, including 21% with grade 3 disease. Patients in the EBRT cohort were slightly younger (median, 74 vs. 75 years; P < .01) and had fewer T1a tumors (11% vs. 13%; P = .02). Histologic grades 1, 2, and 3 comprised 36%, 50%, and 14% of the cohort, respectively, and there were no differences in EBRT utilization by grade. Utilization of EBRT decreased following the publication of the CALGB trial in 2004 decreasing from 82% to 85% in 1998 to 2000 to 73% to 75% in 2005 to 2007 (P < .01). Unadjusted outcomes showed that in grade 1 disease, there were no differences in CSS with or without EBRT at 5 (99%) and 10 years (95%-96%). EBRT was associated with an improvement in CSS in grade 2 histology at 5 years (97% vs. 98%) and 10 years (92% vs. 95%) (P = .004). The benefit was more pronounced in grade 3 disease with CSS increasing from 93% to 96% at 5 years and from 87% to 92% at 10 years (P = .02) with EBRT. In the grade 3 subgroup, propensity-score matching confirmed EBRT was associated with superior CSS compared with surgery alone (hazard ratio, 0.58; 95% confidence interval, 0.34-0.98; P = .043). Conclusion: In this database analysis, omission of radiotherapy after BCS in elderly women with favorable-risk, early stage, grade 3 breast cancer was associated with inferior CSS. Further prospective data in this patient population are needed to confirm our findings and conclusions. Grade 3 disease was not well-represented in clinical trials investigating the omission of radiotherapy following breast conserving surgery in elderly women with early stage breast cancer. This Surveillance, Epidemiology, and End Results analysis of 12,036 women aged 70 to 79 years with T1N0, estrogen receptor-positive, invasive ductal carcinoma found that women with grade 3 disease had both an overall survival and breast cancer-specific mortality benefit with radiotherapy.

Background: Financial toxicity is commonly reported by cancer patients, but few studies have assessed caregiver perceptions. We aimed to validate the modified Comprehensive Score for Financial Toxicity (COST) in cancer caregivers, identify factors associated with financial toxicity in both patients and caregivers, and assess the association of caregiver financial toxicity with patient and caregiver outcomes. Methods: Using a convenience sampling method, 100 dyads of adult cancer patients and a primary caregiver visiting outpatient oncology clinics (Jan–Sep 2019) were recruited. We assessed the internal consistency and convergent and divergent validity of the modified COST. Multivariable analyses identified correlates of financial toxicity. Association of financial toxicity with care non-adherence, lifestyle-altering behaviors (e.g., home refinance/sale, retirement/saving account withdrawal), and quality of life (QOL) was investigated. Results: Recruited patient vs. caregiver characteristics were as follows: mean age: 60.6 vs. 56.5; 34% vs. 46.4% female; 79% vs. 81.4% white. The caregiver COST measure demonstrated high internal consistency (Cronbach α = 0.91). In patients, older age (B, 0.3 [95% CI, 0.1–0.4]) and higher annual household income (B, 14.3 [95% CI, 9.3–19.4]) correlated with lower financial toxicity (P < 0.05). In caregivers, lower patient financial toxicity (B, 0.4 [95% CI, 0.2–0.6]) and cancer stages 1–3 (compared to stage 4) (B, 4.6 [95% CI, 0.4–8.8]) correlated with lower financial toxicity (P < 0.05). Increased caregiver financial toxicity correlated with higher care non-adherence in patients, increased lifestyle-altering behaviors, and lower QOL in patients and caregivers (P < 0.05). Conclusion: The COST measure can also be used to assess caregiver financial toxicity. Caregivers’ financial toxicity was associated with negative outcomes for both dyad members.

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.

Patients in both the 1-10 group and the 11-18 group had good prognoses. Those who experienced recurrence were more likely to be premenopausal and to have failed to comply with the recommended endocrine therapy regimen. Endocrine therapy remains important in these patients. Introduction: Hormone receptor–positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancers without lymph node metastasis have good prognosis. We compared the prognosis of hormone receptor–positive, HER2-negative, lymph node–negative cancers with Oncotype DX score ranges of 1 to 10 (1-10 group) and 11 to < 18 (11-18 group). Patients and Methods: A total of 107 cases in the 1-10 group and 225 cases in the 11-18 group were reviewed. All patients received surgery. The use of chemotherapy, radiotherapy, and endocrine therapy, and overall survival (OS), disease-free survival (DFS), and distant metastasis were compared between groups. Results: There were no statistical differences in the use of chemotherapy (5.05% vs. 6.05%, P =.724) or radiotherapy (52.53% vs. 59.07%, P =.276) between the 1-10 group and the 11-18 group, respectively. The median OS and DFS were 47 and 45 months, respectively, in the 1-10 group, and 49 and 48 months in the 11-18 group. No significant difference was seen in OS (P =.995), DFS (P =.148), or rates of metastasis (P =.998). The 11-18 group had more death events and distant metastasis (death, 5 events; recurrence, 2 events; metastasis, 2 events) than the 1-10 group (death, 0 events; recurrence, 4 events; metastasis, 0 events). The majority of recurrences seen in both groups were in young patients who failed to comply with their endocrine therapy regimen. Conclusion: Patients in both the 1-10 group and the 11-18 group had good prognoses. Those who experienced recurrence were more likely to be premenopausal and to have failed to comply with the recommended endocrine therapy regimen. Endocrine therapy remains important in these patients.

Purpose: Resistance to platinum-based chemotherapy or PARP inhibition in germline BRCA1 or BRCA2 mutation carriers may occur through somatic reversion mutations or intragenic deletions that restore BRCA1 or BRCA2 function. We assessed whether BRCA1/2 reversion mutations could be identified in circulating cell-free DNA (cfDNA) of patients with ovarian or breast cancer previously treated with platinum and/or PARP inhibitors. Experimental Design: cfDNA from 24 prospectively accrued patients with germline BRCA1 or BRCA2 mutations, including 19 patients with platinum-resistant/refractory ovarian cancer and five patients with platinum and/or PARP inhibitor pretreated metastatic breast cancer, was subjected to massively parallel sequencing targeting all exons of 141 genes and all exons and introns of BRCA1 and BRCA2. Functional studies were performed to assess the impact of the putative BRCA1/2 reversion mutations on BRCA1/2 function. Results: Diverse and often polyclonal putative BRCA1 or BRCA2 reversion mutations were identified in cfDNA from four patients with ovarian cancer (21%) and from two patients with breast cancer (40%). BRCA2 reversion mutations were detected in cfDNA prior to PARP inhibitor treatment in a patient with breast cancer who did not respond to treatment and were enriched in plasma samples after PARP inhibitor therapy. Foci formation and immunoprecipitation assays suggest that a subset of the putative reversion mutations restored BRCA1/2 function. Conclusions: Putative BRCA1/2 reversion mutations can be detected by cfDNA sequencing analysis in patients with ovarian and breast cancer. Our findings warrant further investigation of cfDNA sequencing to identify putative BRCA1/2 reversion mutations and to aid the selection of patients for PARP inhibition therapy.

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.

Extrarenal Wilms’ tumor of the ovary is a very rare tumor likely derived from embryonic mesonephros. We present the first reported case of a teratoid extrarenal Wilms’ tumor of the ovary with a short review of the existing literature. In the case, a 26-year-old woman presented with back pain and was found to have a dermoid cyst; three years later, she presented again, now pregnant, with severe abdominal pain. She was diagnosed with an immature teratoma consisting of a Wilms’ tumor (immature component) arising within a mature teratoma and treated exclusively with surgery and surveillance. The recovery from surgery was uneventful and the patient remains without evidence of disease with eleven months of follow-up.