Assessment and Response to Neoadjuvant Treatments in Breast Cancer: Current Practice, Response Monitoring, Future Approaches and Perspectives.

Neoadjuvant treatments (NAT) for breast cancer (BC) consist in the administration of chemotherapy-more rarely endocrine therapy-before surgery. Firstly, it was introduced 50 years ago to downsize locally advanced (inoperable) BCs. NAT are now widespread and so effective to be used also at the early stage of the disease. NAT are heterogeneous in terms of therapeutic patterns, class of used drugs, dosage, and duration. The poly-chemotherapy regimen and administration schedule are established by a multi-disciplinary team, according to the stage of disease, the tumor subtype and the age, the physical status, and the drug sensitivity of BC patients. Consequently, an accurate monitoring of treatment response can provide significant clinical advantages, such as the treatment de-escalation in case of early recognition of complete response or, on the contrary, the switch to an alternative treatment path in case of early detection of resistance to the ongoing therapy. Future is going toward increasingly personalized therapies and the prediction of individual response to treatment is the key to practice customized care pathways, preserving oncological safety and effectiveness. To gain such goal, the development of an accurate monitoring system, reproducible and reliable alone or as part of more complex diagnostic algorithms, will be promising.

Contrast-Enhanced Mammography Versus MRI in the Evaluation of Neoadjuvant Therapy Response in Patients With Breast Cancer: A Prospective Study.

BACKGROUND. Contrast-enhanced mammography (CEM) is rapidly expanding as a credible alternative to MRI in various clinical settings. OBJECTIVE. The purpose of this study was to compare CEM and MRI for neoadjuvant therapy (NAT) response assessment in patients with breast cancer. METHODS. This prospective study included 51 patients (mean age, 46 ± 11 [SD] years) with biopsy-proven breast cancer who were candidates for NAT from May 2015 to April 2018. Patients underwent both CEM and MRI before, during, and after NAT (pre-NAT, mid-NAT, and post-NAT, respectively). Post-NAT CEM included a 6-minute delayed acquisition. One breast radiologist with experience in CEM reviewed CEM examinations; one breast radiologist with experience in MRI reviewed MRI examinations. The radiologists assessed for the presence of an enhancing lesion; if an enhancing lesion was detected, its size was measured. RECIST version 1.1 response assessment categories were derived. Pathologic complete response (pCR) was defined as absence of both invasive cancer and ductal carcinoma in situ (DCIS). RESULTS. Of 51 patients, 16 achieved pCR. CEM yielded systematically lower size measurements compared with MRI (mean difference, -0.2 mm for pre-NAT, -0.7 mm for mid-NAT, and -0.3 mm for post-NAT). All post-NAT imaging tests yielded systematically larger size measurements compared with pathology (mean difference, 0.8 mm for CEM, 1.2 mm for MRI, and 1.9 mm for delayed CEM). Of 12 patients with residual DCIS, an enhancing lesion was detected in seven on post-NAT CEM, eight on post-NAT MRI, and nine on post-NAT delayed CEM. Agreement of RECIST response categories between CEM and MRI, expressed as kappa coefficient, was 0.791 at mid-NAT and 0.871 at post-NAT. For detecting pCR by post-NAT imaging, sensitivity and specificity were 81% and 83% for CEM, 100% and 86% for MRI, and 81% and 89% for delayed CEM. Sensitivity was significantly higher for MRI than CEM (p = .001) and delayed CEM (p = .002); remaining comparisons were not significant (p > .05). CONCLUSION. After NAT for breast cancer, CEM and MRI yielded comparable assessments of lesion size (both slightly overestimated vs pathology) and RECIST categories and showed no significant difference in specificity for pCR. MRI had higher sensitivity for pCR. Delayed CEM acquisition may help detect residual DCIS. CLINICAL IMPACT. Although MRI remains the preferred test for NAT response monitoring, the findings support CEM as a useful alternative when MRI is contraindicated or not tolerated.

Effect of implementing digital breast tomosynthesis (DBT) instead of mammography on population screening outcomes including interval cancer rates: Results of the Trento DBT pilot evaluation.

BACKGROUND/AIM: The Trento screening program transitioned to digital breast tomosynthesis (DBT) screening based on evidence that DBT improves breast cancer (BC) detection compared to mammography; an evaluation of the transition to DBT is reported in this pilot study. METHODS: Prospective implementation of DBT screening included women aged ≥50 years who attended the Trento program for biennial screening. DBT screening included DBT acquisitions with synthesized 2D-images. A historical cohort of women who attended the program (January 2013-October 2014) and received digital mammography (DM) provided a comparison group. Independent double-reading (with a third arbitrating read for discordance) was used for DBT and DM screening. Screening outcomes included cancer detection rate (CDR/1000 screens), percentage of screens recalled to assessment (recall%), interval cancer rate (ICR/1000 screens) at 2-year follow-up, and screening sensitivity. Rate ratios (RR) and 95% confidence interval (95%CI) examined outcomes for DBT versus DM screening. RESULTS: From women aged 50-69 years who accepted an invitation to screening (October 2014-October 2016) 46,343 comprised the DBT-screened group: amongst these 402 BCs (includes 50 ductal carcinoma in-situ (DCIS)) were detected (CDR 8.67/1000), whereas 205 BCs (includes 33 DCIS) were detected amongst 37,436 DM screens (CDR 5.48/1000) [RR for CDR:1.58 (1.34-1.87)]. Recall% was lower for DBT (2.55%) than DM (3.21%) [RR:0.79 (0.73-0.86)]. Compared to DM, DBT screening increased CDR for stage I-II BC, for all tumour size and grade categories, and for node-negative BC, but did not increase CDR for DCIS. Estimated ICR for DBT was 1.1/1000 whereas ICR for DM was 1.36/1000 [RR:0.81 (0.55-1.19)]. Screening sensitivity was 88.74% for DBT versus 80.08% for DM [RR:1.11 (0.94-1.31)]. CONCLUSION: DBT significantly improved early-detection measures but did not significantly reduce ICR (relative to DM screening), suggesting that it could add benefit as well as adding over-detection in population BC screening.

Agreement between digital breast tomosynthesis and pathologic tumour size for staging breast cancer, and comparison with standard mammography.

PURPOSE: Tomosynthesis is proposed to improve breast cancer assessment and staging. We compared tomosynthesis and mammography in estimating the size of newly-diagnosed breast cancers. METHODS: All pathologically-confirmed cancers detected in the STORM-2 trial (90 cancers, 85 women) were retrospectively measured on tomosynthesis by two independent readers. One reader also measured cancers on mammography. Relative mean differences (MDs) and 95% limits of agreement (LOA) with pathology were estimated for tomosynthesis and mammography within a single reader (Analysis 1) and between two readers (Analysis 2). RESULTS: Where cancers were detected and hence measured by both tests, tomosynthesis overestimated pathologic size relative to mammography (Analysis 1: MD 5% versus 1%, Analysis 2: 7% versus 3%; P = 0.10 both analyses). There was similar, large measurement variability for both tests (LOA range: -60% to +166%). Overestimation by tomosynthesis was attributable to the subgroup with dense breasts (MDs = 12-13% versus 4% for mammography). There was low average bias for both tests in the low-density subgroup (MDs = 0-4%). LOA were larger in dense breasts for both tomosynthesis and mammography (P ≤ 0.02 all comparisons). Cancers detected only by tomosynthesis were more frequently in dense breasts (60-68%): for those tumours size was estimated with increased measurement variability (LOA ranging from -75% to +293%). CONCLUSIONS: On average, tomosynthesis overestimates pathologic tumour size in women with dense breasts; that difference is more likely to impact management in women with larger tumours. The main advantage of tomosynthesis appears to be detecting mammographically-occult cancers; however tomosynthesis less accurately measured those cancers in dense breasts (large measurement variability).

Breast conserving treatment for ductal carcinoma in situ in the elderly: can radiation therapy be avoided? Our experience.

INTRODUCTION: Ductal Carcinoma In Situ (DCIS) is a heterogeneous, pre-malignant disease accounting for 15-20% of all new breast cancers. If appropriately managed, DCIS has a small chance of impacting on patient life expectancy. Despite the possibility of a further recurrence or of a development in an invasive form, we are unable to select treatment of choice especially in the elderly. In particularly we risk an overtreatment of women at low risk of progression to invasive breast cancer. The aim of this study was to retrospectively evaluate the outcome of elderly patients affected by DCIS not undergoing Radiation Therapy (RT) after Breast Conserving Surgery (BCS). MATERIAL AND METHODS: We reviewed our prospectively-maintained database from 1998 to 2013, selecting all women over 65 years old diagnosed with DCIS who did not receive RT for personal choice. We considered two groups, according to the risk of local recurrence (Low Risk (Group 1) vs. High Risk (Group 2)). RESULTS: We identified 44 cases of DCIS treated with surgery alone or with surgery followed by adjuvant tamoxifen. 24 patients presented low risk of local recurrence (Group 1) and 20 had characteristics associated to high risk of local recurrence (Group 2). At a median follow-up of 66.3 months, no local recurrences have been described in group 1. No patients presented distant metastases, while 4 patients died for other causes. At a median follow-up of 72 months we observed 5 local recurrences in the second group (p < 0.05). CONCLUSION: Our results suggest that radiation therapy can be safely avoided in a selected group of elderly patients affected by DCIS.

Axillary masses in a woman with a history of breast cancer: dermatopathic lymphadenopathy.

The presence of axillary enlarged lymph nodes in the follow-up of a woman with a history of breast cancer should always be thoroughly indagated. Dermatopathic lymphadenopathy presents a specific pathologic pattern found within the lymph nodes and is usually associated with cutaneous rashes. Patients with various skin conditions can develop regional lymphadenopathy, which can result in the asymptomatic enlargement of the lymph nodes, especially in the inguinal, axillary and cervical regions. Dermatopathic lymphadenopathy should be considered in the differential diagnosis also in patients with minimal cutaneous findings. Dermatopathic lymphadenopathy is a benign process and management of these patients consists in simple clinical, mammographic and ultrasonographic follow-up.

Increase of mastectomy rates after preoperative MRI in women with breast cancer is not influenced by patients age.

Preoperative magnetic resonance imaging (MRI) is increasingly used for staging women with breast cancer, including screening for occult ipsilateral or contralateral cancer. If breast-conserving surgery is planned, a MRI examination should be performed in all ages women with suspected breast cancer, especially those exhibiting dense or heterogeneously dense breast parenchyma, for which the sensitivity of both ultrasonography and mammography is low. MRI staging causes more extensive breast surgery in a significative proportion of women by identifying additional cancer. If the ability to find additional occult cancer is the true value of MRI, this is not influenced by patients' ages. For this reason, preoperative MRI should be counseled to all women with breast cancer by clinicians, independently from the age, as the age alone does not preclude additional findings.