RAF1 gene fusions are recurrent driver events in infantile fibrosarcoma-like mesenchymal tumors.

Infantile fibrosarcomas (IFS) and congenital mesoblastic nephroma (CMN) are rare myofibroblastic tumors of infancy and early childhood commonly harboring the ETV6::NTRK3 gene fusion. IFS/CMN are considered as tumors with an 'intermediate prognosis' as they are locally aggressive, but rarely metastasize, and generally have a favorable outcome. A fraction of IFS/CMN-related neoplasms are negative for the ETV6::NTRK3 gene rearrangement and are characterized by other chimeric proteins promoting MAPK signaling upregulation. In a large proportion of these tumors, which are classified as IFS-like mesenchymal neoplasms, the contributing molecular events remain to be identified. Here, we report three distinct rearrangements involving RAF1 among eight ETV6::NTRK3 gene fusion-negative tumors with an original histological diagnosis of IFS/CMN. The three fusion proteins retain the entire catalytic domain of the kinase. Two chimeric products, GOLGA4::RAF1 and LRRFIP2::RAF1, had previously been reported as driver events in different cancers, whereas the third, CLIP1::RAF1, represents a novel fusion protein. We demonstrate that CLIP1::RAF1 acts as a bona fide oncoprotein promoting cell proliferation and migration through constitutive upregulation of MAPK signaling. We show that the CLIP1::RAF1 hyperactive behavior does not require RAS activation and is mediated by constitutive 14-3-3 protein-independent dimerization of the chimeric protein. As previously reported for the ETV6::NTRK3 fusion protein, CLIP1::RAF1 similarly upregulates PI3K-AKT signaling. Our findings document that RAF1 gene rearrangements represent a recurrent event in ETV6::NTRK3-negative IFS/CMN and provide a rationale for the use of inhibitors directed to suppress MAPK and PI3K-AKT signaling in these cancers. © 2024 The Pathological Society of Great Britain and Ireland.

Outcomes of atypical lobular hyperplasia managed by active surveillance or immediate surgery.

BACKGROUND: Atypical lobular hyperplasia (ALH) is typically diagnosed via needle core biopsy (NCB) and is commonly removed surgically in light of upgrade to malignancy rates of 1%-5%. As studies on radiographic outcomes of ALH managed by active surveillance (AS) are limited, we investigated the upgrade rates of surgically excised ALH as well as radiographic progression during AS. METHODS: In this retrospective study, 125 patients with 127 ALH lesions diagnosed via NCB at Weill Cornell Medicine from 2015 to 2021 were included. The upgrade rate to cancer was determined for patients who had surgical management ≤6 months after biopsy. Among patients with ALH managed by AS, we investigated radiographic progression on 6-month interval imaging. RESULTS: Of 127 ALH lesions, 75% (n = 95) were immediately excised and 25% (n = 32) were observed under AS. The upgrade rate of immediately excised ALH was 2.1% (n = 2; invasive ductal carcinoma [IDC], T1N0 and IDC, and T1Nx). In the AS cohort, no ALH lesions progressed radiographically during the follow-up period of 22.5 months (median), with all remaining stable (50%, n = 16), resolving (47%, n = 15), or decreasing in size (3%, n = 1). CONCLUSIONS: In this study, NCB-diagnosed ALH had a low upgrade to malignancy rate (2.1%), and no ALH lesions managed by AS progressed radiographically during the follow-up period of 22.5 months. These results support AS as the favorable option for patients with pure ALH on biopsy, with surgical excision for lesions that progress on surveillance.

Survival Outcomes in Women with Unilateral, Triple-Negative, Breast Cancer Correlated with Contralateral Prophylactic Mastectomy.

BACKGROUND: Despite increased utilization of contralateral prophylactic mastectomy (CPM), there is insufficient evidence that it improves survival in average-risk women with unilateral breast cancer. CPM may be of heightened interest to patients with triple negative breast cancer (TNBC) because these patients are more likely to have BRCA1 mutation-associated disease and are not candidates for the chemoprevention benefits of adjuvant endocrine therapy. METHODS: Survival and recurrence outcomes were evaluated for all TNBC patients from a multi-institutional database (1999-2018) at two academic cancer programs in two metropolitan cities of the Northeast and Midwest. Median follow-up time was 3.7 years. RESULTS: Seven hundred and nighty six TNBC patients were evaluated and 15.45% underwent CPM. Women undergoing CPM were more likely to be white (p < 0.001), younger (p < 0.001), and underwent genetic testing (p < 0.001). A borderline survival benefit was observed for TNBC patients undergoing CPM (5-year overall survival 95.1% vs. 85.0%; p = 0.05). There was no difference in survival when BRCA mutation carriers were excluded (5-year overall survival 94.1% vs. 85.2%; p = 0.12). For BRCA mutation carriers, a numeric trend was observed for improved survival for patients undergoing CPM (5-year overall survival 97.2% vs. 84.1%; p = 0.35). Among patients not undergoing CPM, the rate of developing a new primary breast cancer was 2.2% (15/673). Among these 15 patients, 20% (3/15) were known BRCA mutation carriers. CONCLUSIONS: Our data demonstrate no survival benefit for TNBC patients without BRCA1/2 mutations undergoing CPM.

Psychosocial well-being during the COVID-19 pandemic among women with and without breast cancer.

OBJECTIVE: Treatment delays in combination with general social distancing practices to reduce transmission may have negative impacts on the mental health of women with breast cancer who may need more social and emotional support. We sought to elucidate the psychosocial effects of the COVID-19 pandemic among women with and without breast cancer in New York City. METHODS: We conducted a prospective cohort study among women aged 18+ across the spectrum of breast health care at New York Presbyterian (NYP)-Weill Cornell, NYP-Brooklyn Methodist Hospital and NYP-Queens. Women were contacted between June and October 2021 to assess their self-reported depression, stress, and anxiety during the COVID-19 pandemic. We compared women who were recently diagnosed, those with a history of breast cancer, and women without cancer whose other health visits were delayed during the pandemic. RESULTS: There were 85 women who completed the survey. Breast cancer survivors (42%) were the least likely to report a delay in care due to COVID compared to breast cancer patients who were recently diagnosed (67%) and women without cancer (67%). Compared to women without cancer and breast cancer survivors, women recently diagnosed with breast cancer reported higher levels of anxiety and depression with a statistically significant difference in perceived stress. CONCLUSIONS: Our findings highlight the need to identify and risk-stratify patients facing a new breast cancer diagnosis in and around the COVID-19 pandemic who may benefit from additional resources to mitigate the adverse impacts of the pandemic and a breast cancer diagnosis on psychosocial health.

Benefit of adjuvant chemotherapy in node-negative T1a versus T1b and T1c triple-negative breast cancer.

PURPOSE: National comprehensive cancer network guidelines recommend delivery of adjuvant chemotherapy in node-negative triple-negative breast cancer (TNBC) if the tumor is > 1 cm and consideration of adjuvant chemotherapy for T1b but not T1a disease. These recommendations are based upon sparse data on the role of adjuvant chemotherapy in T1a and T1b node-negative TNBC. Our objective was to clarify the benefits of chemotherapy for patients with T1N0 TNBC, stratified by tumor size. METHODS: We performed a retrospective analysis of survival outcomes of TNBC patients at two academic institutions in the United States from 1999 to 2018. Primary tumor size, histology, and nodal status were based upon surgical pathology. The Kaplan-Meier plot and 5-year unadjusted survival probability were evaluated. RESULTS: Among 282 T1N0 TNBC cases, the status of adjuvant chemotherapy was known for 258. Mean follow-up was 5.3 years. Adjuvant chemotherapy was delivered to 30.5% of T1a, 64.7% T1b, and 83.9% T1c (p < 0.0001). On multivariable analysis, factors associated with delivery of adjuvant chemotherapy were tumor size and grade 3 disease. Improved overall survival was associated with use of chemotherapy in patients with T1c disease (93.2% vs. 75.2% p = 0.008) but not T1a (100% vs. 100% p = 0.3778) or T1b (100% vs. 95.8% p = 0.2362) disease. CONCLUSION: Our data support current guidelines indicating benefit from adjuvant chemotherapy in node-negative TNBC associated with T1c tumors but excellent outcomes were observed in the cases of T1a and T1b disease, regardless of whether adjuvant chemotherapy was delivered.

Intraductal Papilloma of the Breast: Prevalence of Malignancy and Natural History Under Active Surveillance.

BACKGROUND: The optimal management of intraductal papillomas (IPs) without atypia diagnosed on needle core biopsy (NCB) is unclear. This study analyzed the malignancy risk of immediately excised IPs and characterized the behavior of IPs under active surveillance (AS). METHODS: We retrospectively reviewed the pathology and imaging records of patients diagnosed with IPs without atypia on NCB during a 10-year period (1999-2019). The malignancy upgrade rate was assessed in patients who had an immediate surgical excision, and the rates of both radiographic progression and development of malignancy were assessed in a cohort of patients undergoing AS. RESULTS: The inclusion criteria were met in 152 patients with 175 IPs with a mean age of 51 ± 13 years. The average size of the IPs on initial imaging was 8 ± 4 mm. Most of the lesions (57%, n = 99) were immediately excised, whereas 76 (43%) underwent AS with interval imaging with a median follow-up period of 15 months (range, 5-111 months). Among the immediately excised IPs, surgical pathology revealed benign findings in 97% (n = 96) and ductal carcinoma in situ in 3% (n = 3). In the AS cohort, 72% (n = 55) of the IPs remained stable, and 25% (n = 19) resolved or decreased in size. At 2 years, 4% had increased in size on imaging and were subsequently excised, with ductal carcinoma in situ (DCIS, n = 1) and benign pathology (n = 1) noted on final pathology. CONCLUSIONS: In a large series of breast IPs without atypia, no invasive carcinoma was observed after immediate excision, and 96% of the lesions had not progressed on AS. This suggests that patients with IP shown on NCB can safely undergo AS, with surgery reserved for radiographic lesion progression.

Radial Scars and Complex Sclerosing Lesions of the Breast: Prevalence of Malignancy and Natural History Under Active Surveillance.

BACKGROUND: When needle core biopsies (NCBs) of the breast reveal radial scar or complex sclerosing lesions (RSLs), excision is often recommended despite a low risk of malignancy in the modern era. The optimal management of NCBs revealing RSLs is controversial, and understanding of the natural history of unresected RSLs is limited. METHODS: We retrospectively analyzed pathology and imaging data from 148 patients with NCB revealing RSL without atypia from 2015 to 2019 to determine the prevalence of malignancy and the behavior of RSLs undergoing active surveillance (AS). RESULTS: The mean age of patients was 52 years, and most lesions were screen-detected (91%). The median lesion size was 6.0 mm (range 2-39). Most patients (66%, n = 98) underwent immediate surgery, while 34% (n = 50) of patients underwent AS, with a median follow-up of 16 months (range 6-51). Of the excised RSLs, 99% (n = 97) were benign and 1% (n = 1) revealed ductal carcinoma in situ (DCIS). In 17% (n = 17) of cases, additional high-risk lesions were discovered upon excision. Among the 50 patients undergoing AS, no lesions progressed on interval imaging. CONCLUSIONS: In this cohort, 99% of RSLs undergoing excision were benign, 1% revealed DCIS, and there were no invasive cancers. In the first study of patients with RSLs undergoing AS, we found that all lesions either remained stable or resolved. We propose that the vast majority of patients with RSL on NCB can be safely offered AS, and that routine excision is a low-value intervention.

Fibroepithelial Lesions (FELs) of the Breast: Is Routine Excision Always Necessary?

BACKGROUND: When needle core biopsies (NCBs) of the breast reveal fibroepithelial lesions (FELs), excision is often performed to rule out a phyllodes tumor (PT), despite low malignancy rates. Consequently, the natural history of observed FELs is not well described. We analyzed the malignancy risk in excised FELs and the natural history of FELs undergoing active surveillance (AS). METHODS: We retrospectively studied the pathology and imaging records of 215 patients with FELs (n = 252) diagnosed on NCB. Incidence of growth was determined by Kaplan-Meier method. RESULTS: Of 252 FELs, 80% were immediately excised and 20% underwent AS. Of the excised FELs, 198 (98%) were benign: fibroadenoma (FA) or benign breast tissue in 137 (68%), benign PT in 59 (29%), or LCIS in 2 (1%). Borderline PT or malignant lesions were found in 4 (2%). On ultrasound, malignant and borderline PTs were larger than benign lesions [median 3.9 vs 1.3 cm, p = 0.006]. Fifty FELs underwent AS, with a median follow-up of 17 (range 2-79) months. The majority remained stable or decreased in size: at 2 years, only 35% increased in volume by ≥ 50%. Of those tumors undergoing AS that were later excised (n = 4), all were benign. CONCLUSIONS: Almost all FELs (98%) were benign on surgical excision, and the majority undergoing AS remained stable, with benign pathology if later excised. Most FELs on NCB can be safely followed with US, with surgery reserved for patients with FELs that are large, symptomatic, or growing. This could spare most women with FELs unnecessary surgery.

Universal Use of Intraoperative Nerve Monitoring by Recently Fellowship-Trained Thyroid Surgeons is Common, Associated with Higher Surgical Volume, and Impacts Intraoperative Decision-Making.

INTRODUCTION: The value of routine use of intraoperative recurrent laryngeal nerve monitoring (IONM) in thyroid surgery is controversial. We analyzed the practices of recently fellowship-trained thyroid surgeons from two diverging surgical backgrounds with respect to IONM. We hypothesized that the majority of recently trained surgeons would use IONM, and that it would potentially influence their operative procedure. METHODS: A 21-question survey was sent to 56 fellowship-trained endocrine and head and neck surgeons who completed fellowships accredited by the American Association of Endocrine Surgeons or American Head and Neck Society within the past 10 years, examining the demographics of respondents, and details of IONM practice. Groups were compared using the Fisher exact and χ (2) tests. RESULTS: The response rate for the survey was 76 % (42/56). Overall, 95 % use IONM for some or all of their cases. Sixty percent (n = 25) of respondents always use IONM during thyroid surgery, 36 % (n = 15) use it selectively, and 5 % (n = 2) never use it. We compared respondents who always use IONM (n = 25), to those who selectively or never use it (n = 17). Exposure to IONM during residency or fellowship did not influence use (p = 0.99). However, higher-volume surgeons were more likely to always use IONM (p = 0.036). Among users of IONM, the most common reason given for use was increased surgeon confidence (55 %) and improved safety (54 %). Over 90 % of respondents found reoperative cases and preoperative vocal cord paralysis to be indications for IONM. Among those who always used IONM, 64 % would alter extent of surgery based on IONM findings, compared to only 27 % of selective users. CONCLUSIONS: A survey of recently trained endocrine and head and neck surgeons reveals that the vast majority (95 %) of these surgeons commonly use IONM during thyroid surgery. IONM was more commonly used by higher-volume surgeons. Routine users were more likely to modify surgery based on nerve integrity (i.e., not complete a total thyroidectomy if the nerve loses conduction signal).

Wide Inter-institutional Variation in Performance of a Molecular Classifier for Indeterminate Thyroid Nodules.

BACKGROUND: The Afirma gene expression classifier (GEC) is used to assess malignancy risk in indeterminate thyroid nodules (ITNs) classified as Bethesda category III/IV. Our objective was to analyze GEC performance at two institutions with high thyroid cytopathology volumes but differing prevalence of malignancy. METHODS: Retrospective analysis of all ITNs evaluated with the GEC at Memorial Sloan Kettering Cancer Center (MSK; n = 94) and Mount Sinai Beth Israel (MSBI; n = 71). These institutions have differing prevalences of malignancy in ITNs: 30-38 % (MSK) and 10-19 % (MSBI). Surgical pathology was correlated with GEC findings for each matched nodule. Performance characteristics were estimated using Bayes Theorem. RESULTS: Patient and nodule characteristics were similar at MSK and MSBI. The GEC-benign call rates were 38.3 % (MSK) and 52.1 % (MSBI). Of the GEC-benign nodules, 8.3 % (MSK) and 13.5 % (MSBI) were treated surgically. Surgical pathology indicated that all of GEC-benign nodules were benign. Of the GEC-suspicious nodules, 60.0 % (MSK) and 61.7 % (MSBI) underwent surgery. Positive predictive values (PPVs) for GEC-suspicious results were 57.1 % (95 % CI 41.0-72.3) at MSK and 14.3 % (95 % CI 0.2-30.2) at MSBI. The estimated negative predictive values (NPVs) were 86-92 % at MSK and 95-98 % at MSBI. CONCLUSIONS: There were wide variations in the Afirma GEC-benign call rate, PPV, and NPV between MSBI (a comprehensive health system) and MSK (a tertiary referral cancer center), which had differing rates of malignancy in ITNs. The GEC could not routinely alter management in either institution. We believe that this assay would be expected to be most informative in practice settings where the prevalence of malignancy is 15-21 %, such that NPV >95 % and PPV >25 % would be anticipated. Knowing the prevalence of malignancy in ITNs at a particular institution is critical for reliable interpretation of GEC results.

Skin cancer screening recommendations by U.S. cancer centers: Inconsistency with national guidelines.

OBJECTIVE: The incidence of melanoma has increased dramatically over the past four decades, while overall mortality has remained stable. This increase in incidence without a change in overall mortality may be due to overdiagnosis through skin cancer screening. Despite the USPSTF citing insufficient evidence for or against professional skin cancer screening in average-risk adults, U.S. skin cancer screening practices may be leading to overdiagnosis of skin cancers. METHODS: Two reviewers examined the online recommendations for skin cancer screening of 1113 U.S. cancer centers accredited by the Commission on Cancer, including 66 designated by the National Cancer Institute (NCI). Recommendations on skin cancer screening, such as age, frequency, and patient population (i.e. high-risk of developing skin cancer, "people of color") were documented. RESULTS: We found that 18% of centers (202) recommended professional screening in average-risk adults, 35.8% (399) advised regular self-examination, and only 3.4% (38) cited insufficient evidence for screening practices; 49% of NCI centers (32/66) recommended screening in high-risk adults compared to 13% of non-NCI centers (135/1047; p = 0.0004); 0.45% of centers (5) mentioned the potential harms of screening, while 3.5% (39) specifically recommended screening for people of color. CONCLUSION: Our study reveals that many U.S. cancer centers advise some form of skin cancer screening despite a lack of evidence for or against these practices. Few centers mentioned the potential harms of screening, including overdiagnosis. This indicates a need for stronger evidence for specific screening guidelines and for greater public awareness of the potential benefits and harms of routine skin cancer screening.

Public cervical cancer screening recommendations from US cancer centers: Assessing adherence to national guidelines.

Though widespread adoption of cervical cancer screening (CCS) in the US has been associated with a reduction in cervical cancer incidence and mortality, screening also carries with it potential risks. Newer national guidelines recommend decreased screening frequency to optimize the benefit/risk balance and to prevent over-screening. Here, we examined the alignment of US cancer center websites' public recommendations on CCS with national guidelines. We reviewed the websites of 1024 cancer centers accredited by the US Commission on Cancer during January-August 2022. We recorded the recommended frequency and type of CCS and any screening risks mentioned, comparing against national US Preventive Service Task Force (USPSTF) and American Cancer Society (ACS) guidelines. Of 1024 US cancer centers, 60% (610) provided CCS recommendations. Most centers are in alignment with the screening starting age (96%, 544/565) and stopping age (94%, 440/470) recommended by national guidelines. Of 508 centers specifying the frequency of standalone cervical cytology, 83% (419) recommended a screening interval of three years; however, 14% (73) recommended cervical cytology more frequently than the three-year interval recommended by the ACS/USPSTF. Screening risks were mentioned by 20% (124/610) of centers. Our findings highlight the importance of education on screening benefits and risks for physicians and patients to enable shared decision making based on evidence-based guidelines.

RAS-Mutated Cytologically Indeterminate Thyroid Nodules: Prevalence of Malignancy and Behavior Under Active Surveillance.

Background: Genomic profiling is now available for risk stratification of cytologically indeterminate thyroid nodules (ITNs). Mutations in RAS genes (HRAS, NRAS, KRAS) are found in both benign and malignant thyroid nodules, although isolated RAS mutations are rarely associated with aggressive tumors. Because the long-term behavior of RAS-mutant ITNs is not well understood, most undergo immediate surgery. In this multicenter retrospective cohort study, we characterize tumor growth kinetics of RAS-mutant ITNs followed with active surveillance (AS) using serial ultrasound (US) scans and examine the histopathologic diagnoses of those surgically resected. Methods: US and histopathologic data were analyzed retrospectively from two cohorts: (1) RAS-mutant ITNs managed with AS at three institutions (2010-2023) and (2) RAS-mutant ITNs managed with immediate surgery at two institutions (2016-2020). AS cohort subjects had ≥3 months of follow-up and two or more US scans. Cumulative incidence of nodule growth was determined by the Kaplan-Meier method and growth by ≥72% change in tumor volume. Pathological diagnoses for the immediate surgery cohort were analyzed separately. Results: Sixty-two patients with 63 RAS-mutated ITNs under AS had a median diameter of 1.7 cm (interquartile range [IQR] 1.2-2.6) at time of diagnosis. During a median AS period of 23 months (IQR 9.5-53.5 months), growth was observed in 12 of 63 nodules (19.0%), with a cumulative incidence of 1.9% (1 year), 23.0% (3 years), and 28.0% (5 years). Most nodules (81.0%) demonstrated stability. Surgery was ultimately performed in 6 nodules, of which 1 (16.7%) was malignant. In the cohort of 209 RAS-mutant ITNs triaged to immediate surgery, 33% were malignant (23.9% American Thyroid Association [ATA] low-risk cancers, 7.2% ATA intermediate-risk, and 1.9% ATA high-risk. During a median follow-up of 6.9 (IQR 4.4-7.1) years, there were no disease-specific deaths in these patients. Conclusions: We describe the behavior of RAS-mutant ITNs under AS and find that most demonstrate stability over time. Of the resected RAS-mutant nodules, most were benign; of the cancers, most were ATA low-risk. Immediate surgical resection of all RAS-mutant ITNs appears to be a low-value practice. Further research is needed to help define cases most appropriate for AS or immediate surgery.

Diagnostic Scrutiny and Patterns of Elevated Cancer Risk: Uncovering Overdiagnosis Through Standardized Incidence Ratios.

Certain medical diagnoses and environmental or occupational exposures may be associated with elevated risk of cancer diagnosis, either through causal mechanisms or via increased detection of a subclinical reservoir through increased diagnostic scrutiny (overdiagnosis). The present study aimed to investigate the distribution of elevated cancer risks associated with different diagnoses and exposures. A systematic literature search was conducted to identify studies published in the last 30 years that examined the standardized incidence ratio (SIR) associated with exposures and risk factors. Meta-SIRs for each cancer type were calculated. The distribution of elevated cancer risks was then compared between cancer types previously reported to be susceptible to overdiagnosis and those that have not been associated with overdiagnosis. The review of 108 studies identified four patterns: SIR generally elevated for 1) only overdiagnosis-susceptible cancer types, 2) both overdiagnosed and non-overdiagnosed cancer types, 3) select cancers in accordance with risk factor or exposure, and 4) SIRs that did not exhibit a distinct increase in any cancer type. The distribution of elevated cancer risks may serve as a signature of whether the underlying risk factor or exposure is a carcinogenic process or a mechanism of increased diagnostic scrutiny uncovering clinically occult diseases. The identification of increased cancer risk should be viewed with caution, and analyzing the pattern of elevated cancer risk distribution can potentially reveal conditions that appear to be cancer risk factors but are in fact the result of exposure to medical surveillance or other healthcare activities that lead to the detection of indolent tumors.

Active Surveillance of Atypical Ductal Hyperplasia of the Breast.

BACKGROUND: When needle core biopsy (NCB) of the breast yields atypical ductal hyperplasia (ADH), excision is typically recommended. The natural history of ADH undergoing active surveillance (AS) is not well described. We investigate the rates of upgrade to malignancy of excised ADH and the rates of radiographic progression under AS. MATERIALS AND METHODS: We retrospectively reviewed records of 220 cases of ADH on NCB. Of patients who had surgery within 6 months of NCB, we examined the malignancy upgrade rate. In the AS cohort, we examined rates of radiographic progression on interval imaging. RESULTS: The malignancy upgrade rate among patients who underwent immediate excision (n = 185) was 15.7%: 14.1% (n = 26) ductal carcinoma in situ (DCIS) and 1.6% (n = 3) invasive ductal carcinoma (IDC). Upgrade to malignancy was less common in lesions <4 mm in size (0%) or with focal ADH (5%), and more common among lesions presenting with a radiographic mass (26%). Among the 35 patients who underwent AS, median follow-up was 20 months. Two lesions progressed on imaging (incidence 3.8% at 2 years). One patient without radiographic progression was found to have IDC at delayed surgery. The remaining lesions remained stable (46%), decreased in size (11%), or resolved (37%). CONCLUSIONS: Our findings suggest that AS is a safe approach to managing ADH on NCB for most patients. This could spare many patients with ADH from unnecessary surgery. Given that AS is being investigated for low-risk DCIS in multiple international prospective trials, these results suggest that AS should also be investigated for ADH.

Patterns of immune equilibrium and escape in indolent and progressing tumors.

By comparing indolent/slowly progressing with aggressive/rapidly progressing tumor types, Pandey et al. identify human evidence of immune equilibrium in indolent tumors and immune escape in progressing tumors, suggesting a link between these mechanisms and the epidemiologic phenomenon of overdiagnosis.