Atypical Breast Research Articles

Low-dose tamoxifen for breast cancer prevention in patients with ductal carcinoma in situ (DCIS) and atypical lesions: A real-world experience.

e12537 Background: Patients diagnosed with non-invasive breast lesions such as DCIS and lobular carcinoma in situ (LCIS) and atypical breast lesions such as atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) are at increased risk of developing invasive breast cancer (BC). Tamoxifen 20mg daily for 5 years has shown to be effective for BC prevention in these at-risk patients but its use can be limited by its adverse effects. The recent Tam01 study found that low dose tamoxifen (5mg daily for 3 years) in patients with DCIS, ALH, and ADH resulted in an approximate 50% risk reduction in BC events compared to placebo with a slight increase in hot flashes but no increases in uterine cancer or venous thromboembolism within the tamoxifen group (PMID: 30973790). The objective of this study was to evaluate the use of low dose tamoxifen at our institution and determine how many patients preferred this option. Methods: We performed a retrospective chart review of women who were diagnosed with DCIS, LCIS, ADH, and/or ALH at our institution from January 2019 to December 2021 and subsequently started adjuvant tamoxifen. Patients with history of invasive BC were excluded. Patients were categorized as being on standard dose (20mg daily) or low dose (5mg daily or 10mg every other day) tamoxifen. Fisher’s exact test was used to compare rates of standard and low dose tamoxifen use in the entire cohort as well as in pathology-based subgroups. Results: We included 130 women diagnosed with DCIS, LCIS, ADH and/or ALH and who started adjuvant tamoxifen. The median age at diagnosis was 50 years and 68% were premenopausal. Overall, 62% (n = 80) of women started standard dose tamoxifen and 38% (n = 50) low dose tamoxifen. Among 63 patients who were offered both standard and low dose options, 76% (n = 48) initiated low dose tamoxifen (p < 0.0001). Twenty women were noted to be hesitant to start standard dose tamoxifen due to concern for side effects or preexisting menopausal symptoms but were agreeable to the low dose option. Of the 86 patients with DCIS, a preference for standard dose tamoxifen was observed (74% vs 26%, p = 0.0016). Among 44 patients with LCIS, ADH, and/or ALH, more patients were on low dose tamoxifen (64% vs 36%, p = 0.282). Nine percent (n = 7) of patients on standard dose tamoxifen switched to low dose due to adverse effects including hot flashes, mood changes, and insomnia. Conclusions: At our institution, in patients offered both low dose and standard dose tamoxifen, more than 75% started low dose tamoxifen. The low dose option was more frequently used for atypical lesions such as ADH, ALH and LCIS. In women at higher risk of invasive BC who may be reluctant to start standard dose tamoxifen or intolerant of it, low dose tamoxifen should be considered and offered.

Intraparenchymal breast leiomyoma and atypical leiomyoma

BackgroundBreast leiomyoma is a rare benign mesenchymal tumor, accounting for less than 1% of all breast neoplasms. Cases of breast atypical leiomyoma is even more rarely reported and its diagnostic criteria together with its clinical courses is not cleared defined.Case presentationWe described two patients with breast leiomyomas. One has unilateral benign breast leiomyoma, the other one has bilateral breast leiomyomas. For the bilateral case, the left-side tumor was diagnosed as benign leiomyoma while the right-side tumor was diagnosed as atypical leiomyoma. The morphological features that lead to the diagnosis of atypical leiomyoma are its invasive growth pattern, mild nuclear atypia, and mitotic figures up to 3mitoses/10HPF.ConclusionsAtypical breast leiomyoma appears to behave like benign leiomyoma without recurrence in our study with nine-year follow-up. Due to the limited experience, cases presented as atypical intraparenchymal breast leiomyoma should be closely followed.

Breast angiolipoma in young woman: case report

This case report describes a benign breast tumor, more specifically, an angiolipoma, in a 17-year-old female patient who presented with a nodule in the left breast, painful to palpation. The nodule is at an atypical breast site and has few records in the literature, which were considered in this description that aims at identifying the main histological, ultrasound, mammographic and immunohistochemical characteristics of breast angiolipoma; besides informing other professionals about the possible angiolipoma diagnosis when considering a benign breast tumor, despite its rare occurrence.

Atypical Breast CarcinomaA Series of Six Cases

Breast cancer comprises 10.4% of all cancer among women world and it the second most common type of cancer. Increased public awareness and screening have led to earlier diagnosis at different stages. Surgical resection can be done earlier and complete cure of the disease can be achieved. As a result survival rates for breast cancer in young women have improved significantly. Six unusual type of breast carcinoma, presented to the Surgery Outpatient Department were referred to Pathology Department for further investigations. Patient age and sex, clinical characteristics of the tumour, the duration of the lesion, the size, radiological investigation, Fine Needle Aspiration Cytology (FNAC), trucut biopsy and histopathological examination were noted. Immunohistochemical examination also done in all the cases. Out of the six cases of breast carcinoma, one was the mucinous carcinoma of breast, two invasive papillary breast carcinoma, one apocrine carcinoma, one invasive Pleomorphic Lobular Carcinoma (PLC) of breast and one was fibromatosis like metaplastic carcinoma of breast. All the patients were female except, a 71-year-old male who presented with invasive papillary carcinoma. All the female patients were presented at postmenopausal age group. After careful examination of the cytology and histopathological slides the final diagnosis was made which helped the clinician for further treatment. Rare breast cancers do not differ from other types of breast cancer in their presentation. But they vary by treatment regimens and outcomes. So, proper diagnosis with imaging, FNAC, trucut biopsy and histopathological examination is a combined tool for proper diagnosis and treatment.

Cystic (including atypical) and solid breast lesion classification using the different features of quantitative ultrasound parametric images.

The amount of ultrasound (US) breast examinations continues to grow rapidly because of the wider endorsement of breast cancer screening programs. Cysts are the most commonly diagnosed breast lesions. Atypical breast cysts can be a serious differentiation problem in the US. Our goal was to develop noninvasive automated US grayscale image analysis for the cystic and solid breast lesion differentiation based on mathematical image post-processing. We used a set of 217 ultrasound images of proven 107 cystic (including 53 atypical) and 110 solid lesions. Empirical statistical and morphological models of the lesions were used to obtain features. The AUC indicator and Student's t test were used to assess the quality of the individual features. The Pearson correlation matrix was used to calculate the correlation between various features. The LASSO and stepwise regression methods were used to determine the most significant features. Finally, the lesion classification was carried out by the various methods. The use of LASSO regression for the feature selection made it possible to select the most significant features for classification. The sensitivity increased from 87.1% to 89.2% and the specificity-from 92.2 to 94.8%. After the correlation matrix construction, it was found that features with a high value of the correlation coefficient (0.72; 0.75) can also be used to improve the quality of the classification. The construction of the empirical model of the lesion pixels brightness behavior can provide parameters that are important for the correct classification of ultrasound images. The optimal set of features with the maximum discriminant characteristics may not be consistent with the correlation of features and the value of the AUC index. Features with a low AUC index (in our case 0.72) can also be important for improving the quality of the classification.

Opérer ou non une lésion atypique du sein ? Prise en compte de l’anxiété dans l’aide à la décision partagée à partir d’une cohorte prospective de 300 patientes

IntroductionOrganized and individual breast screening have been accompanied by an increase in the detection of “atypical breast lesions (ABL)”. Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of “low-risk” lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process. MethodsThree hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care. ResultsOne hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, P<0.001) was observed. Anxious temperament and greater intolerance to uncertainty were significantly associated swith decreased anxiety (33%), whereas younger age was associated with increased anxiety (8%). ConclusionSurgery for ABL seems to be associated with only a few cases with an increase in anxiety and seems to increase the perception of the risk of developing breast cancer. Taking into account the psychological dimension remains in all cases essential in the process of shared therapeutic decision.

Macromastia as a Cause of Chronic Back Pain.

Journal of Women's HealthVol. 30, No. 10 Clinical Q & AMacromastia as a Cause of Chronic Back PainSarah A. Layon, Lacey R. Pflibsen, Samantha Maasarani, and Shelley S. NolandSarah A. LayonAddress correspondence to: Sarah A. Layon, BS, Medical School, University of Minnesota Twin Cities, 420 Delaware Street SE, Minneapolis, MN 55455, USA. E-mail Address: layon005@umn.eduhttps://orcid.org/0000-0002-3710-3922Medical School, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.Search for more papers by this author, Lacey R. Pflibsenhttps://orcid.org/0000-0002-1267-5588Division of Plastic Surgery, Mayo Clinic Arizona, Phoenix, Arizona, USA.Search for more papers by this author, Samantha MaasaraniDepartment of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio, USA.Search for more papers by this author, and Shelley S. NolandDivision of Plastic Surgery, Mayo Clinic Arizona, Phoenix, Arizona, USA.Search for more papers by this authorPublished Online:5 Oct 2021https://doi.org/10.1089/jwh.2021.0405AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited byBody mass index and benign breast surgeries: a survey of plastic surgeons’ knowledge and attitudesJPRAS Open, Vol. 15Supportive, Fitted, and Comfortable Bras for Individuals with Atypical Breast Shape/Size: Review of the Challenges and Proposed Roadmap24 October 2022 | Textiles, Vol. 2, No. 4 Volume 30Issue 10Oct 2021 InformationCopyright 2021, Mary Ann Liebert, Inc., publishersTo cite this article:Sarah A. Layon, Lacey R. Pflibsen, Samantha Maasarani, and Shelley S. Noland.Macromastia as a Cause of Chronic Back Pain.Journal of Women's Health.Oct 2021.1372-1374.http://doi.org/10.1089/jwh.2021.0405Published in Volume: 30 Issue 10: October 5, 2021Online Ahead of Print:September 8, 2021PDF download

Abstract 92: Clonal evolution of proliferative lesions into breast cancers

Abstract Introduction: Proliferative lesions in the breast have been implicated in the development of invasive breast cancer. Previous studies showed that adjacent atypical proliferative lesions and breast cancers shared common genetic alterations, suggesting that these evolved from the same ancestral cell. However, the clonal structure of atypical proliferative lesions and their clonal dynamics during progression to cancer are poorly understood. In this study, we compared genetic profiles of proliferative lesions and cancers from the same patients to illustrate the clonal evolution of cancer from a non-malignant epithelial cell. Methods: Multiple samples were collected from various lesions with different disease-level located in the cancer-borne breast, using micro-dissection from formalin-fixed, paraffin-embedded surgical specimens. Somatic mutations and copy number alterations (CNAs) were evaluated by whole exome sequencing. Results: A total of 39 samples from 7 premenopausal females carrying estrogen receptor-positive cancers were analyzed, where the samples were obtained from proliferative lesions (without/with atypia) (N = 3 and 10, respectively), and non-invasive (N = 22) and invasive (N = 4) cancers. The number of somatic mutations per sample increased with disease progression (ranging from 7 to 311). Two cases with bilateral cancers had a pathogenic germline mutation of either BRCA2 or TP53, where no somatic mutations or CNAs were shared by individual proliferative lesions, suggesting multifocal independent cancerous evolutions. By contrast, in the remaining five unilateral cases, no pathogenic germline mutations were detected, but all proliferative lesions, which were separated by a distance of 7 - 70 mm, shared one or more driver alterations, such as an AKT1 mutation, a GATA3 mutation, a CBFB mutation, a PTEN mutation and concurrent 1q gain and 16q loss, while harboring private mutations/CNAs of their own. The analysis of phylogenic trees based on the number of shared mutations predicted an early origin of these founder mutations, which frequently predated decades before the onset of cancer. Conclusions: Our results suggest that early breast cancer development is shaped by the evolution of multiple precancerous clones. In hereditary cases, this process is thought to be substantially promoted multi-focally within the entire breasts, due to innate genomic instability in each mammary epithelial cell for pathogenic germline mutations. By contrast, in sporadic cases, the ancestral cell which has acquired a founder genetic alteration expands macroscopically long before the onset of cancer. These expanded clones work as the niche predisposed to additional mutations, in which branching evolution occurs multi-focally and raises up multiple proliferative lesions, from which invasive cancer finally evolves. Our findings provide unique insight into the early development of breast cancer. Citation Format: Tomomi Nishimura, Nobuyuki Kakiuchi, Kenichi Yoshida, Yasuhide Takeuchi, Hirona Maeda, Yusuke Shiozawa, Masahiro M. Nakagawa, Yotaro Ochi, Yukiko Kawata, Kosuke Aoki, Masahiro Hirata, Tatsuki R. Kataoka, Takaki Sakurai, Satoko Baba, Yuichi Shiraishi, Kenichi Chiba, Kengo Takeuchi, Hironori Haga, Satoru Miyano, Masakazu Toi, Seishi Ogawa. Clonal evolution of proliferative lesions into breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 92.

Contemporary management of atypical breast lesions identified on percutaneous biopsy: a narrative review

: The management of atypical breast lesions identified on core needle biopsy (CNB) for a breast imaging abnormality is a topic of controversy. While all these atypical lesions have routinely been excised in the past, contemporary management requires a multidisciplinary approach that does not have a one-size-fits-all option. Rigorous multidisciplinary review from the breast radiologist and the pathologist should confirm concordance. All discordant biopsies require surgical excision or additional sampling with more aggressive CNB. Concordant biopsies demonstrating pure flat epithelial atypia (FEA), atypical lobular hyperplasia (ALH), and classic type lobular carcinoma in situ (LCIS) should not routinely undergo surgical excision. Of all the atypical breast lesions, atypical ductal hyperplasia (ADH) has the highest risk of upgrade to underlying malignancy and may still be considered for excision, though opportunities for observation for low volume disease may exist. Presentation and extent of atypia, as well as the specific type of atypia should determine the need for excision to rule out underlying malignancy. With the exception of FEA, regardless of whether the site of atypia is excised or not, the patient is also at increased risk of future breast cancer in both breasts. The highest lifetime risk is in women with LCIS. Lifestyle modification, high-risk screening, discussion of chemoprevention, and even bilateral risk-reducing mastectomy may be appropriate for those at a lifetime risk >50%.

Abstract PS14-09: The impact of non-classic LCIS on the natural history of DCIS

Abstract Background: Classic lobular carcinoma in situ (C-LCIS) and non-classic LCIS (NC-LCIS) are histologically and biologically distinct types of lobular neoplasia. Little is known about the impact of NC-LCIS on risk of recurrence when found in association with concomitant malignancy. We sought to assess oncologic outcomes in patients with DCIS and concomitant NC-LCIS as compared to DCIS with concomitant C-LCIS treated with breast conservation. Methods: Upon IRB approval, an institutional database was accessed to identify patients with a diagnosis of C-LCIS + DCIS or NC-LCIS+DCIS in the same core biopsy and/or excisional biopsy specimen. All pathology slides relevant to the diagnosis were confirmed by internal review. Patients with prior or concurrent ipsilateral invasive breast cancer and/or prior ipsilateral DCIS were excluded. Use of adjuvant therapies and the incidence of ipsilateral and contralateral DCIS and invasive breast cancer were compared in the 2 groups. Statistical analysis was performed using the chi-square test. Results: Among patients diagnosed with DCIS between 1996 and 2015 and treated with breast conserving surgery, 69 also had C-LCIS and 13 also had NC-LCIS (the diagnosis of NC-LCIS was not encountered until 2000). Median patient age was 55 years (range 40-88), 42 (51%) had a family history of breast cancer and 5 (6%) had a prior diagnosis of atypical proliferative breast lesions; these factors did not differ between patients with C-LCIS+DCIS and NC-LCIS+DCIS. Patients with NC-LCIS+DCIS were more likely to present with mammographic distortion (25% vs 6%, p=0.03), to have been diagnosed by core biopsy, and less likely to have ER positive (67% vs 91%, p=0.03) or PR positive (50% vs78%, p=0.014) DCIS. In 78% of the patient cohort, final excision margins were negative, and these proportions were not different between the 2 groups The median number of surgeries performed to obtain clear surgical margins which was 2 (range 1-4) for the entire cohort and for C-LCIS+DCIS and NC-LCIS+DCIS, individually. 78.% of C-LCIS+DCIS patients and 54% of NC-LCIS+DCIS patients received adjuvant radiation (p=0.064), and 45% of C-LCIS+DCIS patients took adjuvant hormonal therapy, while none of the NC-LCIS+DCIS patients did (p=0.002). At median follow-up of 78 (1-260) months for C-LCIS+DCIS and 60 (1-197) months for NC-LCIS+DCIS, there were no differences observed in the incidence of ipsilateral and contralateral breast cancer (10.1% vs 7.7% , p=0.19, and 10.1% vs 0%, respectively, p=0.78). One of 13 patients (7.7%) with NC-LCIS+DCIS, who developed an ipsilateral invasive carcinoma, was subsequently diagnosed with bone metastasis. Conclusions: Patients with NC-LCIS+DCIS were more likely to have ER and/or PR negative DCIS and only 54% of this cohort received radiation, yet local-regional recurrence rates were low and not different between NC-LCIS +DCIS and C-LCIS+DCIS patients. Despite the more aggressive histologic features of NC-LCIS, these data do not suggest that NC-LCIS associated with DCIS portends a different prognosis that C-LCIS associated with DCIS. Larger studies are needed to confirm these findings. Citation Format: Faina Nakhlis, Fisher Katlin, Samantha Grossmith, Ashley DiPasquale, Beth Harrison, Tari King. The impact of non-classic LCIS on the natural history of DCIS [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-09.

Section Discrepancy and Diagnostic Performance of Breast Lesions in Two-dimensional Ultrasound by Dynamic Videos versus Static Images

Abstract Background: Benign or malignant breast lesions with typical ultrasonic characteristics could be easily and correctly diagnosed with two-dimensional ultrasound (2D US). However, diagnosis of atypical lesions remains a challenge. Most atypical lesions have different ultrasonographic features with probe direction variation. Thus, the interpretation of ultrasonographic features based on static images empirically collected by sonographers might be inaccurate. We aimed to investigate the section discrepancy and diagnostic performance of breast lesions in 2D US by dynamic videos versus static images. Methods: Static images and dynamic videos based on two perpendicular planes of 468 breast lesions were collected and evaluated. The Breast Imaging and Reporting Data System (BI-RADS®) US lexicon was used. Category 3 was used as the cut-off point, and section discrepancy was defined as two perpendicular planes showing different BI-RADS categories (3 versus 4A, 4B, 4C, and 5). Results: This retrospective study included 315 benign and 153 malignant lesions. There were 53 and 50 lesions with section discrepancy during static and dynamic observations, respectively. The proportion of benign lesions with section discrepancy was significantly higher than that of malignant lesions (P &lt; 0.05) either in dynamic or static observation, and the contingency coefficient was 0.2 between section discrepancy and histopathology. Duct changes were more clearly depicted in dynamic videos than in static images (P &lt; 0.05) both in malignant and benign lesions. Calcification and architectural distortion were more sensitively detected by dynamic videos than with static images (P &lt; 0.05) in malignant lesions. The interpretation of “margin” significantly differed in benign lesions between static images and dynamic videos (P &lt; 0.05). The areas under the curve of static image-horizontal, static image-sagittal, dynamic video-horizontal, and dynamic video-sagittal were 0.807, 0.820, 0.837, and 0.846, respectively. The specificities of dynamic videos were higher than those of static images (P &lt; 0.05). Conclusion: Breast lesions have section discrepancy in 2D US. Observations based on dynamic videos could more accurately reflect lesion features and increase the specificity of US in the differentiation of atypical breast lesions.

Atypical ductal hyperplasia – Benign lesion with malignant potential: A case report

Atypical breast hyperplasia is a precancerous lesion with a high risk of invasive carcinoma. The atypical character of hyperplasia is confirmed by the absence of anti Ck5/6 immuno-marking in the immunohistochemical study. These lesions are difficult to identify on breast ultrasound. Magnetic reas

Fibroadenoma of the Breast

A young woman presented with a breast mass. This lobulated lesion was excised and diagnosed as fibroadenoma.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Which of the following statements regarding breast fibroadenoma is correct?a.Fibroadenomas are most common in post-menopausal women.b.Fibroadenomas may grow rapidly during pregnancy.c.Fibroadenomas are malignant neoplasms.d.Fibroadenomas often recur after complete surgical excision. Answer: b. Fibroadenomas may grow rapidly during pregnancy. Fibroadenoma is a circumscribed benign breast neoplasm.1Neal L. Sandhu N.P. Hieken T.J. Diagnosis and management of benign, atypical, and intermediate breast lesions detected on core needle biopsy.Mayo Clin Proc. 2014; 89: 536-547Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar They occur most commonly in adolescent females and young women, are hormone-sensitive, and may grow rapidly during pregnancy. Fibroadenomas may occur as multiple lesions in a patient, but small fibroadenomas in young women generally have a limited potential for recurrence after complete surgical excision.2Javed A. Jenkins S.M. Labow B. et al.Intermediate and long-term outcomes of fibroadenoma excision in adolescent and young adult patients.Breast J. 2019; 25: 91-95Crossref PubMed Scopus (4) Google Scholar,3Grady I. Gorsuch H. Wilburn-Baily S. Long-term outcome of benign fibroadenomas treated by ultrasound guided percutaneous excision.Breast J. 2008; 14: 275-278Crossref PubMed Scopus (63) Google Scholar

Prospective Multicenter Study Validate a Prediction Model for Surgery Uptake Among Women with Atypical Breast Lesions.

Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting. Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model. The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers. The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH. NCT02523612.

Abstract 4902: Clonal evolution of proliferative lesions into breast cancers

Abstract [Introduction] Proliferative lesions in the breast have been implicated in the development of invasive breast cancer. Previous studies showed that adjacent atypical proliferative lesions and breast cancers shared common genetic alterations, suggesting that these evolved from the same ancestral cell. However, the clonal structure of atypical proliferative lesions and their clonal dynamics during progression to cancer are poorly understood. In this study, we compared genetic profiles of proliferative lesions and cancers from the same patients to illustrate the clonal evolution of cancer from a non-malignant epithelial cell. [Methods] Multiple samples were collected from various lesions with different disease-level located in the cancer-borne breast, using micro-dissection from formalin-fixed, paraffin-embedded surgical specimens. Somatic mutations and copy number alterations (CNAs) were evaluated by whole exome sequencing. [Results] A total of 39 samples from 6 premenopausal females carrying estrogen receptor-positive cancers were analyzed, where the samples were obtained from non-atypical (N = 1) and atypical (N = 8) proliferative lesions, and non-invasive (N = 21) and invasive (N = 4) cancers. The number of somatic mutations per sample increased with disease progression (ranging from 2 to 311). Two cases with bilateral cancers had a pathogenic germline mutation of either BRCA2 or TP53, where no somatic mutations or CNAs were shared by individual proliferative lesions, suggesting multifocal independent cancerous evolutions. By contrast, in the remaining four unilateral cases, no pathogenic germline mutations were detected, but all proliferative lesions, which were separated by a distance of 7 - 70 mm, shared one or more driver alterations, such as an AKT1 mutation, a GATA3 mutation, a CBFB mutation and concurrent 1q gain and 16q loss, while harboring private mutations/CNAs of their own. The analysis of phylogenic trees based on the number of shared mutations predicted an early origin of these founder mutations, which frequently predated decades before the onset of cancer. [Conclusions] Our results suggest that early breast cancer development is shaped by the evolution of multiple precancerous clones. In hereditary cases, this process is thought to be substantially promoted multi-focally within the entire breasts, due to innate genomic instability in each mammary epithelial cell for pathogenic germline mutations. By contrast, in sporadic cases, the ancestral cell which has acquired a founder genetic alteration expands macroscopically long before the onset of cancer, most likely in early adolescent. These expanded clones work as the niche predisposed to additional mutations, in which branching evolution occurs multi-focally and raises up multiple proliferative lesions, from which invasive cancer finally evolves. Our findings provide unique insight into the early development of breast cancer. Citation Format: Tomomi Nishimura, Nobuyuki Kakiuchi, Kenichi Yoshida, Yasuhide Takeuchi, Hirona Maeda, Yusuke Shiozawa, Masahiro M. Nakagawa, Yotaro Ochi, Yukiko Kawata, Kosuke Aoki, Masahiro Hirata, Tatsuki R. Kataoka, Takaki Sakurai, Satoko Baba, Yuichi Shiraishi, Kenichi Chiba, Kengo Takeuchi, Hironori Haga, Satoru Miyano, Masakazu Toi, Seishi Ogawa. Clonal evolution of proliferative lesions into breast cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4902.

Breast Cancer and Secondary Cancer Recurrences After Autologous Tissue Reconstruction

BackgroundThe medical literature defining breast cancer recurrence and secondary cancers after autologous tissue reconstruction for breast cancer is sparse. We sought to identify and analyze occurrences at our institution. Patients and MethodsA 20-year retrospective review of cancer recurrences and atypical breast neoplasms after autologous tissue breast reconstruction at Roswell Park Comprehensive Cancer Center was conducted after being granted a waiver from the institutional review board. ResultsEighteen locoregional recurrences among 337 cases were identified and analyzed. Overall recurrence rate was 5.3%. Four secondary cancers (1.2%) were radiation-induced angiosarcoma, undifferentiated pleomorphic sarcoma, and metaplastic carcinoma. One case of flat epithelial atypia was identified. ConclusionOur retrospective review found incidence and survival after treatment of breast cancer concordant with reports in the literature. We also identified and analyzed secondary neoplasms, including a unique case of undifferentiated pleomorphic sarcoma and metachronous recurrence of breast carcinoma. A case of recurrence as metaplastic carcinoma was identified.

Grayscale Color Mapping with the Mathematical Analysis of an Ultrasound Image in the Differential Diagnosis of Cystic and Solid Breast Masses

Objective. Atypical breast cysts are often quite a serious problem in noninvasive ultrasound differential diagnosis. To develop a system for automated analysis of grayscale ultrasound images, which on the principles of mathematical processing would make it possible to increase the specificity of diagnosis in this situation.Material and methods. The authors developed the CystChecker 1.0 software package. To test this system, they used a set of 217 ultrasound images: 107 cystic (including 53 atypical lesions that were hardly differentially diagnosed by standard methods) and 110 solid (both benign and malignant) breast masses. All the masses were verified by cytology and/or histology. Visual assessment was carried out analyzing grayscale ultrasound, color/power Doppler, and elastography images.Results. Using the system developed by the authors could correctly identify all (n = 107 (100%)) typical cysts, 107 (97.3%) of 110 solid masses, and 50 (94.3%) of 53 atypical cysts. On the contrary, the standard visual assessment provided a possibility of correctly identifying all (n = 107 (100%)) typical cysts, 96 (87.3%) of 110 solid masses, and 32 (60.4%) of 53 atypical cysts (p &lt; 0.05). The corresponding values of the overall specificity of automated and visual assessments were 98 and 87%, respectively.Conclusion. Using the system developed by the authors for automated analysis provides a higher specificity than the visual assessment of an ultrasound image, which is carried out by a qualified specialist.

Do Histopathology and Clinical Outcomes of Breast Atypia Vary by Race/Ethnicity?

BackgroundThe clinical behavior of breast cancer varies by racial and ethnic makeup (REM), but the impact of REM on the clinical outcomes of breast atypia remains understudied. We examined the impact of REM on risk of underlying or subsequent carcinoma following a diagnosis of breast atypia. MethodsIn this retrospective, single-institution chart review, adult women diagnosed with breast atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in situ) were stratified by REM. Regression modeling was used to estimate risk of underlying or subsequent carcinoma. ResultsWe identified 539 patients with breast atypia, including 15 Hispanic (2.8%), 127 non-Hispanic black (23.6%), and 397 non-Hispanic white women (73.7%). Diagnoses included 75.1% atypical ductal hyperplasia (n = 405), 4.6% atypical lobular hyperplasia (n = 25), and 20.2% lobular carcinoma in situ (n = 109). Rates for each type of atypia did not vary by REM (P = 0.33). Of those with atypia on needle biopsy, the rate of underlying carcinoma at excision was 17.3%. After adjustment, REM was not associated with greater risk for carcinoma at excision (P = 0.41). Of those with atypia alone on surgical excision, the rate of a subsequent carcinoma diagnosis was 15.4% (median follow-up 49 mo). REM was not associated with a long-term risk for carcinoma (P = 0.37) or differences in time to subsequent carcinoma (log-rank P = 0.52). Chemoprevention uptake rates were low (10.6%), especially among Hispanic (0%) and non-Hispanic black (3.8%) patients (P = 0.01). ConclusionsAmong patients with atypia, REM does not appear to influence type of histologic atypia, risk for carcinoma, or clinical outcome, despite differences in chemoprevention rates.

The rate of incidental atypical and malignant breast lesions in reduction mammoplasty specimens.

Reduction mammoplasty (RM) is one of the most common plastic surgeries in the United States. We aimed to demonstrate the rate of incidental atypical and malignant breast lesions (AMBL) found in RM specimens and the impact of the number of submitted tissue sections on the rate of AMBL. We analysed our database for patients who had undergone reduction mammoplasty between 2000 and 2018. Patients with a history of breast cancer were excluded from the study. All pathology reports were analysed for AMBL (ALH, LCIS, FEA, ADH, DCIS, invasive carcinoma). The grossing protocol was to submit 10sections from each breast between 2000 and 2013 and six sections between 2014 and 2018. One hundred and sixty-nine of 5208 patients (3.3%) and 216 of 10340 RM specimens (2.1%) showed at least one AMBL. Nineteen (0.36%) patients had incidental cancer. The median age of patients with AMBL was significantly higher than patients without ABL (aged 59years versus 45years). There was no cancer in patients aged <30years. The age-controlled rate of overall AMBL as well as atypia and cancer only did not decrease by submitting fewer sections during the 2014-18 period compared to the 2010-13 period. Decreasing the number of tissue sections from 10 to six did not lead to a significant decrease in the rate of overall AMBL or cancer. Our data suggest that submitting six tissue sections from each breast for patients aged >30years and two sections from each breast for patients aged <30years would be sufficient.

Abstract P4-05-15: Clonal evolution of proliferative lesions into breast cancers

Abstract [Introduction] Proliferative lesions in the breast have been implicated in the development of invasive breast cancer. Previous studies showed that atypical proliferative lesions and adjacent breast cancers shared common genetic alterations, suggesting that these evolved from the same ancestral cell. However, the clonal structure of atypical proliferative lesions and their clonal dynamics during progression to cancer are poorly understood. In this study, we compared genetic profiles of proliferative lesions and cancer tissues from the same patients to illustrate the clonal evolution of cancer from a non-malignant epithelial cell. [Methods] Multiple samples were collected from various lesions with different disease-level located in the cancer-borne breast, including invasive cancers, using micro-dissection from formalin-fixed, paraffin-embedded surgical specimens. Somatic mutations and copy number alterations (CNAs) were then evaluated by whole exome sequencing. [Results] We analyzed a total of 39 samples from 6 premenopausal females carrying estrogen receptor-positive cancers, where the samples were obtained from non-atypical (N = 1) and atypical (N = 8) proliferative lesions, and non-invasive (N = 21) and invasive (N = 4) cancers. The number of somatic mutations per sample ranged from 2 to 311 and increased with disease progression. Two cases with bilateral cancers had a pathogenic germline mutation of either BRCA2 or TP53, where no somatic mutations or CNAs were shared by individual proliferative lesions, suggesting multifocal independent cancerous evolutions. By contrast, in the remaining four unilateral cases, no pathogenic germline mutations were detected, but all proliferative lesions and cancers, which were separated by a distance of 7- 33 mm, shared one or more driver alterations, such as an AKT1 mutation (UID: KU01), a GATA3 mutation (UID: KU03 and KU06), a CBFB mutation (UID: KU06) and concurrent 1q gain and 16q loss (UID: KU02, KU03 and KU06), while harboring private mutations/CNAs of their own. The phylogenetic analysis based on the number of shared mutations predicted an early origin of these founder genetic alterations, which frequently predated decades before the onset of cancer. [Conclusions] Our results suggest that early breast cancer development is shaped by the evolution of multiple precancerous clones. In hereditary cases, this process is thought to be substantially promoted multi-focally within the entire breasts, due to innate genomic instability in each mammary epithelial cell for pathogenic germline mutations. By contrast, in sporadic cases, the ancestral cell which has acquired a founder genetic alteration expands macroscopically long before the onset of cancer, most likely in early adolescent. These expanded clones work as the niche predisposed to additional mutations, in which branching evolution occurs multi-focally and raises up multiple proliferative lesions, from which invasive cancer finally evolves. Our findings provide unique insight into the early development of breast cancer. Citation Format: Tomomi Nishimura, Kenichi Yoshida, Nobuyuki Kakiuchi, Yasuhide Takeuchi, Yukiko Kawata, Hirona Maeda, Yusuke Shiozawa, Kosuke Aoki, Masahiro Hirata, Tatsuki R Kataoka, Takaki Sakurai, Satoko Baba, Yuichi Shiraishi, Kenichi Chiba, Kengo Takeuchi, Hironori Haga, Satoru Miyano, Masakazu Toi, Seishi Ogawa. Clonal evolution of proliferative lesions into breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-05-15.