A computer algorithm that performs at or above the level of radiologists in mammography screening assessment could improve the effectiveness of breast cancer screening.
To perform an external ...evaluation of 3 commercially available artificial intelligence (AI) computer-aided detection algorithms as independent mammography readers and to assess the screening performance when combined with radiologists.
This retrospective case-control study was based on a double-reader population-based mammography screening cohort of women screened at an academic hospital in Stockholm, Sweden, from 2008 to 2015. The study included 8805 women aged 40 to 74 years who underwent mammography screening and who did not have implants or prior breast cancer. The study sample included 739 women who were diagnosed as having breast cancer (positive) and a random sample of 8066 healthy controls (negative for breast cancer).
Positive follow-up findings were determined by pathology-verified diagnosis at screening or within 12 months thereafter. Negative follow-up findings were determined by a 2-year cancer-free follow-up. Three AI computer-aided detection algorithms (AI-1, AI-2, and AI-3), sourced from different vendors, yielded a continuous score for the suspicion of cancer in each mammography examination. For a decision of normal or abnormal, the cut point was defined by the mean specificity of the first-reader radiologists (96.6%).
The median age of study participants was 60 years (interquartile range, 50-66 years) for 739 women who received a diagnosis of breast cancer and 54 years (interquartile range, 47-63 years) for 8066 healthy controls. The cases positive for cancer comprised 618 (84%) screen detected and 121 (16%) clinically detected within 12 months of the screening examination. The area under the receiver operating curve for cancer detection was 0.956 (95% CI, 0.948-0.965) for AI-1, 0.922 (95% CI, 0.910-0.934) for AI-2, and 0.920 (95% CI, 0.909-0.931) for AI-3. At the specificity of the radiologists, the sensitivities were 81.9% for AI-1, 67.0% for AI-2, 67.4% for AI-3, 77.4% for first-reader radiologist, and 80.1% for second-reader radiologist. Combining AI-1 with first-reader radiologists achieved 88.6% sensitivity at 93.0% specificity (abnormal defined by either of the 2 making an abnormal assessment). No other examined combination of AI algorithms and radiologists surpassed this sensitivity level.
To our knowledge, this study is the first independent evaluation of several AI computer-aided detection algorithms for screening mammography. The results of this study indicated that a commercially available AI computer-aided detection algorithm can assess screening mammograms with a sufficient diagnostic performance to be further evaluated as an independent reader in prospective clinical trials. Combining the first readers with the best algorithm identified more cases positive for cancer than combining the first readers with second readers.
High mammographic density is associated with breast cancer and with delayed detection. We have examined whether localized density, at the site of the subsequent cancer, is independently associated ...with being diagnosed with a large-sized or interval breast cancer.
Within a prospective cohort of 63,130 women, we examined 891 women who were diagnosed with incident breast cancer. For 386 women, retrospective localized density assessment was possible. The main outcomes were interval cancer vs. screen-detected cancer and large (> 2 cm) vs. small cancer. In negative screening mammograms, overall and localized density were classified reflecting the BI-RADS standard. Density concordance probabilities were estimated through multinomial regression. The associations between localized density and the two outcomes were modeled through logistic regression, adjusted for overall density, age, body mass index, and other characteristics.
The probabilities of concordant localized density were 0.35, 0.60, 0.38, and 0.32 for overall categories "A," "B," "C," and "D." Overall density was associated with large cancer, comparing density category D to A with OR 4.6 (95%CI 1.8-11.6) and with interval cancer OR 31.5 (95%CI 10.9-92) among all women. Localized density was associated with large cancer at diagnosis with OR 11.8 (95%CI 2.7-51.8) among all women and associated with first-year interval cancer with OR 6.4 (0.7 to 58.7) with a significant linear trend p = 0.027.
Overall density often misrepresents localized density at the site where cancer subsequently arises. High localized density is associated with interval cancer and with large cancer. Our findings support the continued effort to develop and examine computer-based measures of localized density for use in personalized breast cancer screening.
Breast cancer prognosis is strongly associated with tumor size at diagnosis. We aimed to identify factors associated with diagnosis of large (> 2 cm) compared to small tumors, and to examine ...implications for long-term prognosis.
We examined 2012 women with invasive breast cancer, of whom 1466 had screen-detected and 546 interval cancers that were incident between 2001 and 2008 in a population-based screening cohort, and followed them to 31 December 2015. Body mass index (BMI) was ascertained after diagnosis at the time of study enrollment during 2009. PD was measured based on the contralateral mammogram within 3 years before diagnosis. We used multiple logistic regression modeling to examine the association between tumor size and body mass index (BMI), mammographic percent density (PD), or hormonal and genetic risk factors. Associations between the identified risk factors and, in turn, the outcomes of local recurrence, distant metastases, and death (153 events in total) in women with breast cancer were examined using Cox regression. Analyses were carried out according to mode of detection.
BMI and PD were the only factors associated with tumor size at diagnosis. For BMI (≥25 vs. < 25 kg/m
), the multiple adjusted odds ratios (OR) were 1.37 (95% CI 1.02-1.83) and 2.12 (95% CI 1.41-3.18), for screen-detected and interval cancers, respectively. For PD (≥20 vs. < 20%), the corresponding ORs were 1.72 (95% CI 1.29-2.30) and 0.60 (95% CI 0.40-0.90). Among women with interval cancers, those with high BMI had worse prognosis than women with low BMI (hazard ratio 1.70; 95% CI 1.04-2.77), but PD was not associated with the hazard rate. Among screen-detected cancers, neither BMI nor PD was associated with the hazard rate.
In conclusion, high BMI was associated with the risk of having a tumor larger than 2 cm at diagnosis. Among women with interval cancer, high BMI was associated with worse prognosis. We believe that women with high BMI should be especially encouraged to attend screening.
In accordance with European guidelines, mammography screening comprises independent readings by two breast radiologists (double reading). CAD (computer-aided detection) has been suggested to ...complement or replace one of the two readers (single reading + CAD).The aim of this systematic review is to address the following question: Is the reading of mammographic x-ray images by a single breast radiologist together with CAD at least as accurate as double reading?
The electronic literature search included the databases Pub Med, EMBASE and The Cochrane Library. Two independent reviewers assessed abstracts and full-text articles.
1049 abstracts were identified, of which 996 were excluded with reference to inclusion and exclusion criteria; 53 full-text articles were assessed for eligibility. Finally, four articles were included in the qualitative analysis, and one in a GRADE synthesis.
The scientific evidence is insufficient to determine whether the accuracy of single reading + CAD is at least equivalent to that obtained in standard practice, i.e. double reading where two breast radiologists independently read the mammographic images.
Objective: Our purpose was to compare the effects of tibolone, continuous combined hormone replacement therapy, and placebo on mammographic breast density. Study design: A prospective, randomized, ...double-blind placebo-controlled study was performed. A total of 166 postmenopausal women were equally randomized to receive tibolone 2.5 mg, estradiol 2 mg/norethisterone acetate 1 mg (E2/NETA), or placebo. Mammograms were performed at baseline and after 6 months of treatment. Mammographic density was quantified according to the Wolfe classification and by the percentage area of the breast that had a dense pattern. Results: An increase in mammographic density was much more common among women receiving continuous combined hormone replacement therapy (46%-50%) than among those receiving tibolone (2%-6%) and placebo (0%) treatment. The difference between E2/NETA and placebo was highly significant (P < .001). Treatment with tibolone did not differ from that with placebo. The relative risk of an increase in breast density for E2/NETA versus tibolone was found to be 8.3 (95% CI 2.7-25.0). Conclusion: An increase in mammographic density should be regarded as an unwanted side effect of hormone replacement therapy. In contrast to estrogen/progestogen treatment, tibolone seems to exert little stimulation of breast tissue. (Am J Obstet Gynecol 2002;186:717-22.)
Breast cancer outcomes in low- and middle-income countries (LMCs) correlate with the degree to which 1) cancers are detected at early stages, 2) newly detected cancers can be diagnosed correctly, and ...3) appropriately selected multimodality treatment can be provided properly in a timely fashion. The Breast Health Global Initiative (BHGI) invited international experts to review and revise previously developed BHGI resource-stratified guideline tables for early detection, diagnosis, treatment, and healthcare systems. Focus groups addressed specific issues in breast pathology, radiation therapy, and management of locally advanced disease. Process metrics were developed based on the priorities established in the guideline stratification. The groups indicated that cancer prevention through health behavior modification could influence breast cancer incidence in LMCs. Diagnosing breast cancer at earlier stages will reduce breast cancer mortality. Programs to promote breast self-awareness and clinical breast examination and resource-adapted mammographic screening are important early detection steps. Breast imaging, initially with ultrasound and, at higher resource levels with diagnostic mammography, improves preoperative diagnostic assessment and permits image-guided needle sampling. Multimodality therapy includes surgery, radiation, and systemic therapies. Government intervention is needed to address drug-delivery problems relating to high cost and poor access. Guideline dissemination and implementation research plays a crucial role in improving care. Adaptation of technology is needed in LMCs, especially for breast imaging, pathology, radiation therapy, and systemic treatment. Curricula for education and training in LMCs should be developed, applied, and studied in LMC-based learning laboratories to aid information transfer of evidence-based BHGI guidelines.
EUSOBI and 30 national breast radiology bodies support mammography for population-based screening, demonstrated to reduce breast cancer (BC) mortality and treatment impact. According to the ...International Agency for Research on Cancer, the reduction in mortality is 40 % for women aged 50–69 years taking up the invitation while the probability of false-positive needle biopsy is <1 % per round and overdiagnosis is only 1–10 % for a 20-year screening. Mortality reduction was also observed for the age groups 40–49 years and 70–74 years, although with “limited evidence”. Thus, we firstly recommend biennial screening mammography for average-risk women aged 50–69 years; extension up to 73 or 75 years, biennially, is a second priority, from 40–45 to 49 years, annually, a third priority. Screening with thermography or other optical tools as alternatives to mammography is discouraged. Preference should be given to population screening programmes on a territorial basis, with double reading. Adoption of digital mammography (not film-screen or phosphor-plate computer radiography) is a priority, which also improves sensitivity in dense breasts. Radiologists qualified as screening readers should be involved in programmes. Digital breast tomosynthesis is also set to become “routine mammography” in the screening setting in the next future. Dedicated pathways for high-risk women offering breast MRI according to national or international guidelines and recommendations are encouraged.
Key points
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EUSOBI and 30 national breast radiology bodies support screening mammography
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A first priority is double
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reading biennial mammography for women aged 50
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69 years
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Extension to 73
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75 and from 40
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45 to 49 years is also encouraged
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Digital mammography
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not film
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screen or computer radiography
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should be used
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DBT is set to become
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routine mammography
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in the screening setting in the next future
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Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological ...activity and prognosis, offering the possibility for timely response‐guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One‐hundred‐and‐fifty patients with large, operable and locally advanced HER2‐negative breast cancer received epirubicin and docetaxel, with the addition of bevacizumab. Patients underwent tumor biopsies at baseline, after Cycle 2 and at the time of surgery. The primary end point, pCR, and its relation with the secondary endpoints event‐free survival (EFS), overall survival (OS) and gene expression profiles, are reported. The pCR rate was 13% (95% CI 8.6–20.2), with significantly more pCRs among triple‐negative 28% (95% CI 14.8–45.4) than among hormone receptor positive (HR+) tumors 9% (95% CI 4.6–16.3); (OR = 3.9 CI = 1.5–10.3). pCR rates were not associated with EFS or OS. PAM50 subtypes significantly changed after Cycle 2 (p = 0.03) and an index of absolute changes in PAM50 correlations between these time‐points was associated with EFS HR = 0.62 (CI = 0.3–1.1). In univariable analyses, signatures for angiogenesis, proliferation, estrogen receptor signaling, invasion and metastasis, and immune response, measured after Cycle 2, were associated with pCR in HR+ tumors. Evaluation of changes in molecular subtypes and other signatures early in the course of neoadjuvant treatment may be predictive of pCR and EFS. These factors may help guide further treatment and should be considered when designing neoadjuvant trials.
What's new?
It's a good sign for a patient's prognosis if, after pre‐operative chemotherapy, no breast cancer cells survive. But this metric isn't perfect, and varies depending on the tumor's molecular subtype. Here, the authors analyzed changes in gene expression brought on by chemotherapy. They analyzed molecular markers in biopsies from 150 breast cancer patients at three time points: baseline, after 2 cycles of neoadjuvant therapy, and right before surgery. Neoadjuvant chemotherapy significantly changed the tumor's gene expression profile, they found, and these changes could have predictive value: a bigger change between baseline and Cycle 2 correlated with longer event‐free survival.
Breast cancer is serious public health problem in countries of all resource levels. Although major advances in the detection and treatment of the disease have occurred in higher income settings, ...similar progress has been slow or scarce in most low- and middle-income countries (LMCs). The poorer outcomes in LMCs may relate to the limited capability of their healthcare systems (HCS) to provide successful early detection, diagnosis, and treatment of breast cancer. Impediments to better outcomes include insufficient numbers of appropriately trained healthcare workers, limited access to screening/treatment facilities, inadequate supplies of necessary drugs, and timeliness of treatment after diagnosis. Clearly, these HCS deficiencies are broader than the scope of the Breast Health Global Initiative (BHGI) and are not unique to the issue of breast cancer. To address issues in HCS that hinder the delivery of breast health services, the BHGI Healthcare Systems and Public Policy Panel explored the HCS structures and function needed to operate a breast care program (BCP). Like with all BHGI guidelines, those proposed by this panel were expressed in terms of 4 strata of resource levels: basic, limited, enhanced, and maximal. The current report describes the issues and questions related to HCS that are important to consider when designing, implementing, and measuring the performance of a BCP. Health ministers, other policymakers, healthcare personnel, administrators, and anyone else involved in developing a BCP can use and adapt this framework to improve outcomes and ensure the more effective use of resources.
Trastuzumab emtansine (T-DM1) is presently approved for treatment of advanced breast cancer and after incomplete response to neoadjuvant therapy, but the potential of T-DM1 as monotherapy is so far ...unknown.
To assess pathologic complete response (pCR) to standard neoadjuvant therapy of combination docetaxel, trastuzumab, and pertuzumab (DTP) vs T-DM1 monotherapy in patients with ERBB2 (formerly HER2)-positive breast cancer.
This randomized phase 2 trial, conducted at 9 sites in Sweden, enrolled 202 patients between December 1, 2014, and October 31, 2018. Participants were 18 years or older, with ERBB2-positive tumors larger than 20 mm and/or verified lymph node metastases. Analysis was performed on an intention-to-treat basis.
Patients were randomized to receive 6 cycles of DTP (standard group) or T-DM1 (investigational group). Crossover was recommended at lack of response or occurrence of intolerable toxic effects. Assessment with fluorine 18-labeled fluorodeoxyglucose (18F-FDG) positron emission tomography combined with computed tomography (PET-CT) was performed at baseline and after 2 and 6 treatment cycles.
Pathologic complete response, defined as ypT0 or Tis ypN0. Secondary end points were clinical and radiologic objective response; event-free survival, invasive disease-free survival, distant disease-free survival, and overall survival; safety; health-related quality of life (HRQoL); functional and biological tumor characteristics; and frequency of breast-conserving surgery.
Overall, 202 patients were randomized; 197 (99 women in the standard group median age, 51 years (range, 26-73 years) and 98 women in the investigational group median age, 53 years (range, 28-74 years)) were evaluable for the primary end point. Pathologic complete response was achieved in 45 patients in the standard group (45.5%; 95% CI 35.4%-55.8%) and 43 patients in the investigational group (43.9%; 95% CI 33.9%-54.3%). The difference was not statistically significant (P = .82). In a subgroup analysis, the pCR rate was higher in hormone receptor-negative tumors than in hormone receptor-positive tumors in both treatment groups (45 of 72 62.5% vs 45 of 125 36.0%). Three patients in the T-DM1 group experienced progression during therapy. In an exploratory analysis, tumor-infiltrating lymphocytes at 10% or more (median) estimated pCR significantly (odds ratio, 2.76; 95% CI, 1.42-5.36; P = .003). Response evaluation with 18F-FDG PET-CT revealed a relative decrease of maximum standardized uptake value by equal to or greater than 68.7% (median) was associated with pCR (odds ratio, 6.74, 95% CI, 2.75-16.51; P < .001).
In this study, treatment with standard neoadjuvant combination DTP was equal to T-DM1.
ClinicalTrials.gov Identifier: NCT02568839; EudraCT number: 2014-000808-10.
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