Breast imaging screening during lactation poses a real clinical challenge, especially in high-risk patients. We presented the case of a 34-year-old BRCA1-mutated woman showing marked, asymmetric background parenchymal enhancement on the right breast suspicious for malignancy in the context of annual screening magnetic resonance imaging. The patient revealed that she was still occasionally breastfeeding her two-year-old child only from right side. Ultrasound evaluation reported typical benign lactational findings on the right enhancing breast. An in-depth understanding of expected/ physiologic breast changes during lactation and an accurate clinical-radiological correlation are required to appropriately guide patient management and avoid misdiagnosis

Ballesio, Laura

Capri, Oriana

Caruso, Giuseppe

Casinelli, Alice

Malavolta, Giulia

Radiology Case Reports

Archivio della ricerca- Università di Roma La Sapienza

R a d i o l o g y  C a s e  R e p o r t s  1 6  ( 2 0 2 1 )  3 1 0 4 – 3 1 0 8  Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/radcr Case Report Breast imaging screening in a BRCA1-mutated lactating patient: A potential pitfall mimicking malignancy ✩ , ✩✩ , ★ Alice Casinelli, MD a , ∗, Giulia Malavolta, MD a , Giuseppe Caruso, MD b , Oriana Capri, Prof.b , Laura Ballesio, Prof.a a Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Italy b Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Italy a r t i c l e i n f o Article history: Received 31 May 2021 Accepted 10 July 2021 Keywords: Background parenchymal enhancement Breast cancer Breastfeeding Magnetic resonance imaging Ultrasound a b s t r a c t Breast imaging screening during lactation poses a real clinical challenge, especially in high- risk patients. We presented the case of a 34-year-old BRCA1-mutated woman showing marked, asymmetric background parenchymal enhancement on the right breast suspicious for malignancy in the context of annual screening magnetic resonance imaging. The pa- tient revealed that she was still occasionally breastfeeding her two-year-old child only from right side. Ultrasound evaluation reported typical benign lactational findings on the right enhancing breast. An in-depth understanding of expected/ physiologic breast changes dur- ing lactation and an accurate clinical-radiological correlation are required to appropriately guide patient management and avoid misdiagnosis. © 2021 Published by Elsevier Inc. on behalf of University of Washington. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )             Introduction Histological and imaging changes of the breasts during preg-nancy and lactation are not well-understood and still repre-sent a diagnostic challenge for radiologists worldwide. The pe-culiar physiologic breast modifications secondary to the hor-monal changes of pregnancy and lactation result in increased✩ Acknowledgements: The authors have not received any grants. ✩✩ Competing Interest: None. ★ Patient Consent: Written informed consent for publication was obvolving human participants were in accordance with the ethical standwith the 1964 Helsinki declaration and its later amendments or compa∗ Corresponding Author . E-mail address: alicecasinelli@gmail.com (A. Casinelli).  https://doi.org/10.1016/j.radcr.2021.07.019 1930-0433/© 2021 Published by Elsevier Inc. on behalf of University of WBY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )breast volume with associated palpable nodularity, firmness,and parenchymal hyperdensity [1] . These changes may affectclinical and radiologic evaluations of the breasts and poten-tially lead to diagnostic errors. In particular, atypical back-ground parenchymal enhancement (BPE) can be easily misdi-agnosed at first glance, especially in case of high-risk screen-ing imaging (e.g., BRCA-mutated patients). The purpose of this report is to underline the importance ofan accurate radiological-clinical correlation when interpret-tained from the patient. All procedures performed in studies in- ards of the institutional and/or national research committee and rable ethical standards. ashington. This is an open access article under the CC  R a d i o l o g y  C a s e  R e p o r t s  1 6  ( 2 0 2 1 )  3 1 0 4 – 3 1 0 8  3105 Fig. 1 – Mammography in all 3 projections (A. craniocaudal; B. mediolateral oblique; C. laterolateral) showing mild, diffuse, asymmetric increased density of the right breast. Axial T1 weighted (D) and axial T2 weighted (E) fat-suppressed images showing asymmetric increased density of the right breast compared to the left and showing high free water content.                                                       ing breast imaging features of lactating patients, especially incase of high-risk factors (e.g., BRCA mutations). Case presentation A 34-year-old woman with a mutation in BRCA1 gene was ad-mitted to our Breast Imaging Department for annual screeningmammography. The patient skipped her scheduled checkupsin the last two years after she had given birth. Her past medicalhistory was otherwise unremarkable. No signs and symptomswere reported. Mammography was performed in three standard pro-jections and revealed a mild, diffuse increased density ofthe right breast compared to the left, without architecturaldistortions or microcalcifications ( Fig. 1 A-C ). Breast MRI(magnetic resonance imaging) examination was then per-formed in the prone position using a dedicated breast coilwith a 3T system. Axial fat-saturated T2-weighted, axial T2-weighted, DWI (diffusion-weighted imaging) sequences wereobtained. The initial examination proved a diffuse increaseddensity and a high free water content of the right breast( Fig. 1 D-E ), without diffusion restriction in DWI and ADC(apparent diffusion coefficient) mapping ( Fig. 2 ). Dynamiccontrast-enhanced images were obtained using axial andsagittal fat-saturated T1-weighted sequences once before andfive times after the administration of contrast material at 40-second intervals and evaluated on standard subtraction im-ages. The dynamic study demonstrated an early, marked anddiffuse contrast-enhancement of the right breast ( Fig. 3 ). Foranalysis of enhancement kinetics, time-intensity curves wereplotted based on the signal intensity values in a region of in-terest (ROI) in the central region of the right breast on se-rial dynamic images ( Fig. 4 ) and a type 2 curve (“plateau pat-tern”) was obtained. Given mammographic and MRI findings,the patient was also evaluated with US (ultrasound) examina-tion. US images revealed diffuse enlargement of the right glan-dular component with diffuse hyperechogenicity and unilat-eral prominent ductal system as per lactating breast, whereasno significant findings were observed in the left breast( Fig. 5 ). Upon further medical investigation, the patient revealedthat she had been occasionally breastfeeding her two-year-oldchild only from right breast for the past two years; therefore,radiological images were interpreted as benign physiologicalchanges of lactational breast. Discussion We presented an illustrative case of lactational breast radio-logical changes mimicking malignancy in a BRCA-1 mutatedpatient during annual imaging screening. A thorough under-standing of both the anatomy and physiology of the normallactating breast is necessary to properly recognize any poten-tial abnormality while avoiding misdiagnosis. Hormonal changes during pregnancy and lactation are pri-marily responsible for the major physiologic breast structuralchanges. During pregnancy, estrogen and progesterone actsynergistically to stimulate glandular proliferation and differ-entiation, ductal distension and stromal involution, while in-hibiting prolactin and milk production. As estrogen and pro-gesterone levels drop off after delivery, the lactogenic effectof prolactin becomes un-opposed and results in increasedmilk production. Generally, there is a bilateral increased sizeand density and the mammary vascular flow doubles in vol-ume. Involution occurs three months after the suspension ofbreastfeeding [1] . 3106 R a d i o l o g y  C a s e  R e p o r t s  1 6  ( 2 0 2 1 )  3 1 0 4 – 3 1 0 8  Fig. 2 – Axial DWI weighted images (A) and ADC map (B) showing no restriction of diffusion bilaterally and in particular on the right breast. Fig. 3 – Marked, asymmetric BPE at screening MRI imaging. (A-E) Serial dynamic axial contrast-enhanced T1-weighted fat-suppressed images; (F) Sagittal contrast-enhanced T1-weighted fat-suppressed image of the right breast showing unilateral, diffuse rapid contrast enhancement. Fig. 4 – The curve of enhancement “plateau-shaped” (type 2) obtained by kinetics analysis on a ROI put in the retroareolar deep region of the right breast.                             Breast imaging findings during lactation reflect these phys-iologic changes and could mimic breast malignancies, mak-ing radiological evaluations quite challenging. As in our case,breast MRI findings in lactating patients include the follow-ing: (a) increased breast size and density; (b) incremented andrapid BPE due to increased vascularity; (c) diffusely increasedT2 signal secondary to the water content of breast milk. On ul-trasound examination, most breast parenchyma appears hy-perechoic and hypervascularized as a result of combined glan-dular enlargement and milk engorgement [2 ,3] . Breast cancer occurring during gestation, lactation orwithin 1 year from delivery is called pregnancy-associatedbreast cancer (PABC); it accounts for 1%-2 % of all newly diag-nosed breast cancers each year. PABC is generally biologicallyaggressive, being estrogen and progesterone receptor negativeand Her2-neu receptor positive. It is common to overlook, un-derestimate or misdiagnose PABC because of the difficultiesin the clinical evaluation and imaging interpretation of breastdisorders in this period, so it has a poor prognosis and is oftenadvanced at diagnosis [3] . MRI assessment of PABC during lactation is controversialand limited by a high number of false positives. Lactatingparenchyma shows rapid and marked gadolinium uptake sim-ilar to that seen in malignancies, attributed to increased vas-cularity and vascular permeability [4] . BP is the normal con-trast enhancement of fibroglandular breast tissue. The levelof global BPE is assessed in four BI-RADS categories: mini-mal ( < 25% of glandular tissue enhanced), mild (25%-50% ofglandular tissue enhanced), moderate (50%-75% of glandu-lar tissue enhanced) and marked ( > 75% of glandular tissueR a d i o l o g y  C a s e  R e p o r t s  1 6  ( 2 0 2 1 )  3 1 0 4 – 3 1 0 8  3107 Fig. 5 – (A-C) US images of the right breast showing diffuse hyperechogenicity of parenchyma related to the production of milk, which is rich in fat; (C) retroareolar region US image showing a mild prominent ductal system (arrow) due to milk secretion; (D-E) US images of the left breast proving the normal echogenicity of a fibroglandular breast, without pathologic appearances (in the upper internal quadrant there is a benign lesion of 6 mm in size).                                         enhanced) [4] . It is generally mild, bilateral, symmetric, withdiffuse distribution; however, it may be marked, unilateral,asymmetric and these atypical patterns of BPE cause diagnos-tic difficulties because these morphology and temporal degreecan be seen with non-mass enhancement (NME) malignancies[5] . Just as high density decreases the sensitivity of mammog-raphy, so moderate to marked BPE can affect the accuracy ofMRI interpretation [6] . However, Oh et al. [4] suggested con-founders such as increased BPE and T2 signal: in these pa-tients, if cancer does not appear as a lump – i.e., low-signal-intensity mass on T2 weighted images – it can be difficult torecognize a malignancy. As reported by Sabate et al. [6] , US isan appropriate radiologic tool for evaluating breast disordersin pregnancy and lactation because the sonographic semiol-ogy of breast does not change significantly in these women[7-10] . In particular, US has a great sensitivity (nearly 100%) indetection and characterization of palpable breast masses inpregnant and lactating women [9] . In our case, breast imaging screening was even more de-manding since the lactating patient was also BRCA1-mutated.The current breast cancer screening guidelines of the Ameri-can College of Radiology (ACR) states that an annual screeningMRI is appropriate and effective for patients at high risk forbreast cancer including BRCA mutation carriers at the age of25 years, in addition to an annual mammogram at the age of30 years; many of these young women are pregnant or breast-feeding during the time of screening [8 ,10] . ACR guidelines recommend that contrast-enhanced MRIcan be safely performed in lactating women and it is safe forthe mother to continue breastfeeding after receiving gadolin-ium [3 ,7 ,10] . In conclusion, while joining the scant evidences on lacta-tional breast radiological changes, we argue that an under-standing of expected physiologic breast changes during lacta-tion and a careful radiological-clinical correlation are requiredto successfully guide patient management and avoid misdiag-nosis. Ethical statement Written informed consent was obtained from the patient. Allprocedures performed in studies involving human partici-pants were in accordance with the ethical standards of the in-stitutional and/or national research committee and with the1964 Helsinki declaration and its later amendments or com-parable ethical standards. Supplementary materials Supplementary material associated with this article can befound, in the online version, at doi: 10.1016/j.radcr.2021.07.019 .R E F E R E N C E S  [1] Geddes DT . Inside the lactating breast: the latest anatomy research. J Midwifery Womens Health 2007;52(6):556–63 Nov-Dec .[2] Geddes DT . Ultrasound imaging of the lactating breast: methodology and application. Int Breastfeed J 2009;4:4 .[3] Joshi S , Dialani V , Marotti J , Mehta T , Slanetz P . Breast disease in the pregnant and lactating patient: radiological-pathological correlation. Insights Imaging 2013;4(5):527–38 Oct .[4] Oh SW , Lim HS , Moon SM , Kim JW , Shin SS , Heo SH . MR imaging characteristics of breast cancer diagnosed during lactation. Br J Radiol 2017;90(1078):20170203 Oct .3108 R a d i o l o g y  C a s e  R e p o r t s  1 6  ( 2 0 2 1 )  3 1 0 4 – 3 1 0 8  [5] Giess CS , Yeh ED , Raza S . Background parenchymal enhancement at breast MR imaging: normal patterns, diagnostic challenges, and potential for false-positive and false-negative interpretation. Radiographics 2014;34(1):234–47 Jan-Feb .[6] Sabate JM , Clotet M , Torrubia S , Gomez A , Guerrero R , de las Heras P , et al. Radiologic evaluation of breast disorders related to pregnancy and lactation. Radiographics 2007;27(1):S101–24 OctSuppl .[7] Boivin G , de Korvin b B , Marionb J . Is a breast MRI possible and indicated in case of suspicion of breast cancer during lactation? Diagn Interv Imaging 2012;93(11):823–7 .[8] Carmichael H , Matsen C , Freer P , Kohlmann W , Stein M ,Buys SS , et al. Breast cancer screening of pregnant and breastfeeding women with BRCA mutations. Breast Cancer Res Treat 2017;162(2):225–30 Apr .[9] Vashi R , Hooley R , Butler R , Geisel J , Philpotts L . Breast imaging of the pregnant and lactating patient: imaging modalities and pregnancy-associated breast cancer. AJR Am J Roentgenol 2013;200(2):321–8 Feb .[10] American college of radiology (ACR) Breast imaging reporting and data system (BI-RADS). Fifth Edition. Atlas; 2013. http://www.acr.org/birads .

English

Breast imaging screening in a BRCA1-mutated lactating patient: a potential pitfall mimicking malignancy

Alice Casinelli, MD

Giulia Malavolta, MD

Giuseppe Caruso, MD

Oriana Capri, Prof.

Laura Ballesio, Prof.

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Breast imaging screening in a BRCA1-mutated lactating patient: A potential pitfall mimicking malignancy

Breast imaging screening in a BRCA1-mutated lactating patient: a potential pitfall mimicking malignancy

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