Nipple discharge: the state of the art

Over 80% of females experience nipple discharge during their life. Differently from lactational (milk production) and physiological (white, green, or yellow), which are usually bilateral and involving multiple ducts, pathologic nipple discharge (PND) is a spontaneous commonly single-duct and unilateral, clear, serous, or bloody secretion. Mostly caused by intraductal papilloma(s) or ductal ectasia, in 5-33% of cases is due to an underlying malignancy. After clinical history and physical examination, mammography is the first step after 39, but its sensitivity is low (7–26%). Ultrasound shows higher sensitivity (63–100%). Nipple discharge cytology is limited by a false negative rate over 50%. Galactography is an invasive technique that may cause discomfort and pain; it can be performed only when the duct discharge is demonstrated at the time of the study, with incomplete/failed examination rate up to 15% and a difficult differentiation between malignant and benign lesions. Ductoscopy, performed under local anesthesia in outpatients, provides a direct visualization of intraductal lesions, allowing for directed excision and facilitating a targeted surgery. Its sensitivity reaches 94%; however, it is available in only few centers and most clinicians are unfamiliar with its use. PND has recently emerged as a new indication for contrast-enhanced breast MRI, showing sensitivity superior to galactography, with an overall sensitivity up to 96%, also allowing tailored surgery. Surgery no longer can be considered the standard approach to PND. We propose a state-of-the art flowchart for the management of nipple discharge, including ductoscopy and breast MRI as best options

Breast cancer screening programs: does one risk fit all?

Comment on Risk-Adapted Starting Age of Screening for Relatives of Patients With Breast Cancer. [JAMA Oncol. 2019

Clinical utility of gadobenate dimeglumine in contrast-enhanced MRI of the breast: a review

Breast magnetic resonance imaging (MRI) is considered the technique with the highest sensitivity for breast cancer detection. Gadobenate dimeglumine is a gadolinium-based contrast agent (GBCA) that is specifically approved in Europe for breast MRI and which has the highest r1 relaxivity among all GBCAs for this indication. In order to improve the diagnostic performance of breast MRI, several intra-individual crossover studies have evaluated gadobenate dimeglumine as a possible GBCA for this application. This review focuses on the role and advantages of gadobenate dimeglumine as a contrast agent for breast MRI by describing the unique properties of this agent and by summarizing published studies

Changes in total choline concentration in the breast of healthy fertile young women in relation to menstrual cycle or use of oral contraceptives: a 3-T 1H-MRS study

BACKGROUND: To evaluate changes in total choline (tCho) absolute concentration ([tCho]) in the breast of healthy fertile women in relation to menstrual cycle (MC) or use of oral contraceptives (OC). METHODS: After institutional review board approval, we prospectively evaluated 40 healthy fertile volunteers: 20 with physiological MC, aged 28 ± 3 years (mean ± standard deviation; nOC group); 20 using OC, aged 26 ± 3 years (OC group). Hormonal assays and water-suppressed single-voxel 3-T proton magnetic resonance spectroscopy (1H-MRS) were performed on MC days 7, 14, and 21 in the nOC group and only on MC day 14 in the OC group. [tCho] was measured versus an external phantom. Mann-Whitney U test and Spearman coefficient were used; data are given as median and interquartile interval. RESULTS: All spectra had good quality. In the nOC group, [tCho] (mM) did not change significantly during MC: 0.8 (0.3-2.4) on day 7, 0.9 (0.4-1.2) on day 14, and 0.4 (0.2-0.8) on day 21 (p = 0.963). In the OC group, [tCho] was 0.7 (0.2-1.7) mM. The between-groups difference was not significant on all days (p ≥ 0.411). All hormones except prolactin changed during MC (p ≤ 0.024). In the OC group, [tCho] showed a borderline correlation with estradiol (r = 0.458, p = 0.056), but no correlation with other hormones (p ≥ 0.128). In the nOC group, [tCho] negatively correlated with prolactin (r = -0.587, p = 0.006) on day 7; positive correlation was found with estradiol on day 14 (r = 0.679, p = 0.001). CONCLUSIONS: A tCho peak can be detected in the normal mammary gland using 3-T 1H-MRS. The [tCho] in healthy volunteers was 0.4-0.9 mM, constant over the MC and independent of OC use

Can MRI biomarkers predict triple-negative breast cancer?

The purpose of this study was to investigate MRI features of triple-negative breast cancer (TNBC) compared with non-TNBC, to predict histopathological results. In the study, 26 patients with TNBC and 24 with non-TNBC who underwent multiparametric MRI of the breast on a 3 T magnet over a 10-months period were retrospectively recruited. MR imaging sets were evaluated by two experienced breast radiologists in consensus and classified according to the 2013 American College of Radiology (ACR) BI-RADS lexicon. The comparison between the two groups was performed using the Chi-square test and followed by logistic regression analyses. We found that 92% of tumors presented as mass enhancements (p = 0.192). 41.7% of TNBC and 86.4% of non-TNBC had irregular shape (p = 0.005); 58.3% of TNBC showed circumscribed margins, compared to 9.1% of non-TNBC masses (p = 0.001); 75% of TNBC and 9.1% of non-TNBC showed rim enhancement (p < 0.001). Intralesional necrosis was significantly associated with TNBC (p = 0.016). Rim enhancement and intralesional necrosis risulted to be positive predictors at univariate analysis (OR = 29.86, and 8.10, respectively) and the multivariate analysis confirmed that rim enhancement is independently associated with TNBC (OR = 33.08). The mean ADC values were significantly higher for TNBC (p = 0.011). In conclusion, TNBC is associated with specific MRI features that can be possible predictors of pathological results, with a consequent prognostic value

Can unenhanced MRI of the breast replace contrast-enhanced MRI in assessing response to neoadjuvant chemotherapy?

BACKGROUND: The goals of neoadjuvant chemotherapy (NAC) are to reduce tumor volume and to offer a prognostic indicator in assessing treatment response. Contrast-enhanced magnetic resonance imaging (CE-MRI) is an established method for evaluating response to NAC in patients with breast cancer. PURPOSE: To validate the role of unenhanced MRI (ue-MRI) compared to CE-MRI for assessing response to NAC in women with breast cancer. MATERIAL AND METHODS: Seventy-one patients with ongoing NAC for breast cancer underwent MRI before, during, and at the end of NAC. Ue-MRI was performed with T2-weighted sequences with iterative decomposition of water and fat and diffusion-weighted sequences. CE-MRI was performed using three-dimensional T1-weighted sequences before and after administration of gadobenate dimeglumine. Two blinded observers rated ue-MRI and CE-MRI for the evaluation of tumor response. Statistical analysis was performed to compare lesion size and ADC values changes during therapy, as well as inter-observer agreement. RESULTS: There were no statistically significant differences between ue-MRI and CE-MRI sequences for evaluation of lesion size at baseline and after every cycle of treatment ( P > 0.05). The mean tumor ADC values at baseline and across the cycles of NAC were significantly different for the responder group. CONCLUSION: Ue-MRI can achieve similar results to CE-MRI for the assessment of tumor response to NAC. ADC values can differentiate responders from non-responders

Association between growth differentiation factor-15 (GDF-15) serum levels, anorexia and low muscle mass among cancer patients

The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile. GDF-15 serum levels were assessed by ELISA. We enrolled 59 CP and 30 controls; among CP, 25 were affected by gastrointestinal and 34 by lung cancer. Anorexia was present in 36% of CP. Gastrointestinal CP resulted more anorexic compared to lung CP (p = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP (p = 0.049). The GDF-15 levels were higher in CP vs. controls (p = 0.00016), as well as in anorexic vs. non-anorexic CP (p = 0.005) and vs. controls (p < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP (p = 0.0004). No difference was found in GDF-15 between CP with low muscle mass and those with moderate/high muscularity and between patients with body weight loss and those with stable weight. Our data support the involvement of GDF-15 in the pathogenesis of cancer anorexia. The mechanisms of action of GDF-15 in cancer should be further clarified also regarding the changes in muscularity

MRI versus mammography plus ultrasound in women at intermediate breast cancer risk: study design and protocol of the MRIB multicenter, randomized, controlled trial

In women at high/intermediate lifetime risk of breast cancer (BC-LTR), contrast-enhanced magnetic resonance imaging (MRI) added to mammography ± ultrasound (MX ± US) increases sensitivity but decreases specificity. Screening with MRI alone is an alternative and potentially more cost-effective strategy. Here, we describe the study protocol and the characteristics of enrolled patients for MRIB feasibility, multicenter, randomized, controlled trial, which aims to compare MRI alone versus MX+US in women at intermediate breast cancer risk (aged 40-59, with a 15-30% BC-LTR and/or extremely dense breasts). Two screening rounds per woman were planned in ten centers experienced in MRI screening, the primary endpoint being the rate of cancers detected in the 2 arms after 5 years of follow-up. From July 2013 to November 2015, 1254 women (mean age 47 years) were enrolled: 624 were assigned to MX+US and 630 to MRI. Most of them were aged below 50 (72%) and premenopausal (45%), and 52% used oral contraceptives. Among postmenopausal women, 15% had used hormone replacement therapy. Breast and/or ovarian cancer in mothers and/or sisters were reported by 37% of enrolled women, 79% had extremely dense breasts, and 41% had a 15-30% BC-LTR. The distribution of the major determinants of breast cancer risk profiles (breast density and family history of breast and ovarian cancer) of enrolled women varied across centers

Axillary lymphadenopathy at the time of COVID-19 vaccination: ten recommendations from the European Society of Breast Imaging (EUSOBI).

Unilateral axillary lymphadenopathy is a frequent mild side effect of COVID-19 vaccination. European Society of Breast Imaging (EUSOBI) proposes ten recommendations to standardise its management and reduce unnecessary additional imaging and invasive procedures: (1) in patients with previous history of breast cancer, vaccination should be performed in the contralateral arm or in the thigh; (2) collect vaccination data for all patients referred to breast imaging services, including patients undergoing breast cancer staging and follow-up imaging examinations; (3) perform breast imaging examinations preferentially before vaccination or at least 12 weeks after the last vaccine dose; (4) in patients with newly diagnosed breast cancer, apply standard imaging protocols regardless of vaccination status; (5) in any case of symptomatic or imaging-detected axillary lymphadenopathy before vaccination or at least 12 weeks after, examine with appropriate imaging the contralateral axilla and both breasts to exclude malignancy; (6) in case of axillary lymphadenopathy contralateral to the vaccination side, perform standard work-up; (7) in patients without breast cancer history and no suspicious breast imaging findings, lymphadenopathy only ipsilateral to the vaccination side within 12 weeks after vaccination can be considered benign or probably-benign, depending on clinical context; (8) in patients without breast cancer history, post-vaccination lymphadenopathy coupled with suspicious breast finding requires standard work-up, including biopsy when appropriate; (9) in patients with breast cancer history, interpret and manage post-vaccination lymphadenopathy considering the timeframe from vaccination and overall nodal metastatic risk; (10) complex or unclear cases should be managed by the multidisciplinary team

Breast MRI: EUSOBI recommendations for women's information.

UNLABELLED: This paper summarizes information about breast MRI to be provided to women and referring physicians. After listing contraindications, procedure details are described, stressing the need for correct scheduling and not moving during the examination. The structured report including BI-RADS® categories and further actions after a breast MRI examination are discussed. Breast MRI is a very sensitive modality, significantly improving screening in high-risk women. It also has a role in clinical diagnosis, problem solving, and staging, impacting on patient management. However, it is not a perfect test, and occasionally breast cancers can be missed. Therefore, clinical and other imaging findings (from mammography/ultrasound) should also be considered. Conversely, MRI may detect lesions not visible on other imaging modalities turning out to be benign (false positives). These risks should be discussed with women before a breast MRI is requested/performed. Because breast MRI drawbacks depend upon the indication for the examination, basic information for the most important breast MRI indications is presented. Seventeen notes and five frequently asked questions formulated for use as direct communication to women are provided. The text was reviewed by Europa Donna-The European Breast Cancer Coalition to ensure that it can be easily understood by women undergoing MRI. KEY POINTS: • Information on breast MRI concerns advantages/disadvantages and preparation to the examination • Claustrophobia, implantable devices, allergic predisposition, and renal function should be checked • Before menopause, scheduling on day 7-14 of the cycle is preferred • During the examination, it is highly important that the patient keeps still • Availability of prior examinations improves accuracy of breast MRI interpretation.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00330-015-3807-