Ki-67 evaluation using deep-learning model-assisted digital image analysis in breast cancer.

AIMS: To test the efficacy of artificial intelligence (AI)-assisted Ki-67 digital image analysis in invasive breast carcinoma (IBC) with quantitative assessment of AI model performance. METHODS AND RESULTS: This study used 494 cases of Ki-67 slide images of IBC core needle biopsies. The methods were divided into two steps: (i) construction of a deep-learning model (DL); and (ii) DL implementation for Ki-67 analysis. First, a DL tissue classifier model (DL-TC) and a DL nuclear detection model (DL-ND) were constructed using HALO AI DenseNet V2 algorithm with 31,924 annotations in 300 Ki-67 digital slide images. Whether the class predicted by DL-TC in the test set was correct compared with the annotation of ground truth at the pixel level was evaluated. Second, DL-TC- and DL-ND-assisted digital image analysis (DL-DIA) was performed in the other 194 luminal-type cases and correlations with manual counting and clinical outcome were investigated to confirm the accuracy and prognostic potential of DL-DIA. The performance of DL-TC was excellent and invasive carcinoma nests were well segmented from other elements (average precision: 0.851; recall: 0.878; F1-score: 0.858). Ki-67 index data and the number of nuclei from DL-DIA were positively correlated with data from manual counting (ρ = 0.961, and 0.928, respectively). High Ki-67 index (cutoff 20%) cases showed significantly worse recurrence-free survival and breast cancer-specific survival (P = 0.024, and 0.032, respectively). CONCLUSION: The performances of DL-TC and DL-ND were excellent. DL-DIA demonstrated a high degree of concordance with manual counting of Ki-67 and the results of this approach have prognostic potential.

Unusual presentation of breast adenoid cystic carcinoma resembling adenomyoepithelioma with multiple distinct foci.

We describe an unusual case of multifocal breast adenoid cystic carcinoma (AdCC) with adenomyoepitheliomatous morphology. Most breast AdCCs are unifocal and only four cases of multifocal AdCC have been reported previously, however, to our best knowledge, multifocality in AdCC confirmed by molecular analysis has not been reported, so this report adds to the literature on this unique presentation. An 80-year-old woman presented with a left breast mass at 1 o'clock and non-mass enhancement lesion at 5 o'clock on imaging. Incisional biopsy at 1 o'clock showed AdCC based on histopathological features and MYB rearrangement by fluorescent in situ hybridization (FISH). As AdCC involved the margins and the non-mass enhancing lesion remained, mastectomy was performed. Microscopically, the lesion at 5 o'clock demonstrated multinodularity and a biphasic epithelial-basaloid/myoepithelial pattern. Although histological features resembled adenomyoepithelioma, MYB rearrangement was identified on FISH, so the 5 o'clock lesion was also diagnosed as AdCC showing an adenomyoepitheliomatous pattern. This unusual presentation is a potential diagnostic pitfall, so pathologists should consider AdCC as a possible differential diagnosis of multifocal basaloid breast tumors with adenomyoepitheliomatous features.

Bilateral oncoplastic breast-conserving surgery with volume replacement technique using the omental flap: a case report.

BACKGROUND: Many oncoplastic volume replacement techniques have been reported, however, it is generally difficult to utilize a single distant flap for bilateral breast carcinomas. CASE PRESENTATION: We report a case of bilateral multiple breast carcinomas successfully treated with immediate volume replacement technique with an omental flap. Bilateral partial mastectomies were performed for bilateral breast carcinomas (one in the left breast and two in the right breast). The pedicled omental flap was laparoscopically harvested, and divided at the mid-portion of the flap. The proximal half of the flap was used to fill the right defect, and the distal half of the flap filled two defects in the left breast. Cosmetic outcome was excellent with minimal donor-site scars. CONCLUSIONS: The omental flap can be considered for highly selected patients with bilateral breast carcinomas.

Predictive value of ductal carcinoma in situ with invasive breast cancer in core needle biopsies for final pathologic size of intraductal elements.

Preoperative evaluations of the size of ductal carcinoma in situ (DCIS) extension in invasive breast cancer (IBC) are problematic and markers of the actual size of DCIS remain elusive. This study aimed to quantify DCIS on core needle biopsy (CNB) and investigated its association with degree of DCIS extension on paired resection specimens, instead of with presence or absence of an extensive intraductal component or margin status as in earlier studies. This series examined 150 IBCs diagnosed from paired CNB and resection specimens. The DCIS/invasion ratio was calculated using the sum of each element size from CNB. In resection specimens, cases in which the greatest dimension of DCIS extension was longer than the greatest dimension of invasive size were defined as extended DCIS (Ext-DCIS). DCIS/invasion ratio level correlated positively with the degree of Ext-DCIS (P = 0.003). Using receiver operating characteristic curve analysis, setting cases with the subgroup of DCIS extension with greatest dimension > 2.5 times that of the invasive size in the resection specimen (Ext-DCIS > 2.5) as the positive class provided the best discrimination ability for DCIS/invasion ratio (0.375). In multivariate analysis, DCIS/invasion ratio > 0.375 was significantly associated with Ext-DCIS > 2.5 (P = 0.033). In conclusion, DCIS/invasion ratio > 0.375 in CNB was identified as a predictor of Ext-DCIS > 2.5 in resection specimens, suggesting that an approach combining DCIS/invasion ratio from CNB with preoperative staging may better predict the extent of DCIS and facilitate better surgical planning.

Spiradenoma of the breast: a rare diagnostic pitfall in the evaluation of solid-basaloid breast lesions with a dual cell population.

Breast spiradenoma is extremely rare, with only 4 cases reported previously. We describe an instructive case of breast spiradenoma resembling adenoid cystic carcinoma (AdCC). A 71-year-old woman underwent excisional biopsy of a breast mass after a conclusive diagnosis was unable to be obtained from core needle biopsy showing an AdCC-like pattern. Histopathologically, the lesion demonstrated solid and cribriform foci comprising basaloid cells, luminal cells, and eosinophilic hyaline material, reminiscent of solid-basaloid AdCC, alongside convoluted lumens, stromal edema, lymphocytic infiltration, and c-kit negativity. On molecular analysis, neither MYB fusion genes nor CYLD gene abnormalities were identified. These results were supportive of spiradenoma. Salivary gland- and skin adnexal-type tumors are challenging to diagnose due to morphological overlaps. This case, highlighting histopathological and molecular features, shows that breast spiradenoma can be a diagnostic pitfall among the differential diagnoses of AdCC.

Fat necrosis in level I oncoplastic breast-conserving surgery focusing on a modified round block technique.

The modified round block technique (MRBT) is a level I oncoplastic breast-conserving surgery (OBCS), which contains a very wide glandular flap created by extensive dual-plane undermining that is achieved by entire subcutaneous dissection and approximately 50% dissection of the breast parenchyma from the pectoralis muscle. A retrospective analysis was performed for 100 patients who underwent OBCS using MRBT from February 2009 to October 2017. The incidence of positive margin was 7.0% (seven cases), and there has been no local recurrence during a median follow-up period of 68 months. Short- and long-term complications included fat necrosis (11.0%), infection (4.0%), and hematoma formation (4.0%). When patients were divided into two groups based upon the preoperative mammography findings, fat necrosis occurred in 5.2% of the patients with extremely dense or heterogeneously dense mammography, and in 19.0% of patients with scattered fibroglandular or entire fat mammography, which showed a statistically significant difference. Therefore, in level I OBCS, the extent of dual-plane undermining should be minimized to less than 50% of the total parenchyma in fatty breasts.

Quantitative digital image analysis of tumor-infiltrating lymphocytes in HER2-positive breast cancer.

As visual quantification of the density of tumor-infiltrating lymphocytes (TILs) lacks in precision, digital image analysis (DIA) approach has been applied in order to improve. In several studies, TIL density has been examined on hematoxylin and eosin (HE)-stained sections using DIA. The aim of the present study was to quantify TIL density on HE sections of core needle biopsies using DIA and investigate its association with clinicopathological parameters and pathological response to neoadjuvant chemotherapy in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The study cohort comprised of patients with HER2-positive breast cancer, all treated with neoadjuvant anti-HER2 therapy. DIA software applying machine learning-based classification of epithelial and stromal elements was used to count TILs. TIL density was determined as the number of TILs per square millimeter of stromal tissue. Median TIL density was 1287/mm2 (range, 123-8101/mm2). A high TIL density was associated with higher histological grade (P = 0.02), estrogen receptor negativity (P = 0.036), and pathological complete response (pCR) (P < 0.0001). In analyses using receiver operating characteristic curves, a threshold TIL density of 2420/mm2 best discriminated pCR from non-pCR. In multivariate analysis, high TIL density (> 2420/mm2) was significantly associated with pCR (P < 0.0001). Our results indicate that DIA can assess TIL density quantitatively, machine learning-based classification algorithm allowing determination of TIL density as the number of TILs per unit area, and TIL density established by this method appears to be an independent predictor of pCR in HER2-positive breast cancer.

A Genome-Wide Association Study Identifies Five Novel Genetic Markers for Trastuzumab-Induced Cardiotoxicity in Japanese Population.

Trastuzumab has been administered to patients with human epidermal growth factor receptor 2 (HER2)-positive cancer, however, the cardiotoxicity is identified as one of the life-threatening toxicities. Clinically useful biomarker for trastuzumab-induced cardiotoxicity has been expected to be developed. To identify a novel genetic marker(s) determining the risk of trastuzumab-induced cardiotoxicity, we performed a first genome-wide association study (GWAS) in Japanese population. We enrolled 481 patients who had been treated with trastuzumab and carried out a GWAS using 11 cases (with cardiotoxicity) and 257 controls (without cardiotoxicity). Top 100 single nucleotide polymorphisms (SNPs) which revealed the smallest p values in GWAS (p = 7.60 × 10-7 - 2.01 × 10-4) were further examined using replication samples consisted of 14 cases and 199 controls. The combined analysis of the GWAS and replication study indicated possible association of five loci with trastuzumab-induced cardiotoxicity (rs9316695 on chromosome 13q14.3, rs28415722 on chromosome 15q26.3, rs7406710 on chromosome 17q25.3, rs11932853 on chromosome 4q25, and rs8032978 on chromosome 15q26.3, Pcombined = 6.00 × 10-6, 8.88 × 10-5, 1.07 × 10-4, 1.42 × 10-4, 1.60 × 10-4, respectively). Furthermore, we developed a risk prediction model for trastuzumab-induced cardiotoxicity using the five marker SNPs. The incidence of trastuzumab-induced cardiotoxicity in patients with risk score ≥5 was significantly higher (42.5%) compared to that in patients with score ≤ 4 (1.8%) (p = 7.82 × 10-15, odds ratio = 40.0). These findings suggest the potential to improve the ability of physicians to avoid the trastuzumab-induced cardiotoxicity for patients with HER2-positive cancer.

Oncoplastic surgery with omental flap reconstruction: a study of 200 cases.

BACKGROUND: There are several small case series on use of a laparoscopically harvested omental flap (LHOF) for breast reconstruction. However, the long-term oncological safety and clinical benefits of the LHOF remain uncertain, especially in use of the flap in oncoplastic breast surgery. STUDY DESIGN: A retrospective chart review was performed for 200 patients who underwent oncoplastic breast surgery using a LHOF at our institution from April 2002 to March 2016. Laparoscopy-associated complications, local recurrence, and cosmetic outcomes were evaluated. RESULTS: Most of the patients underwent partial breast reconstruction immediately after breast-conserving surgery (BCS). The success rate of laparoscopic harvesting of the omental flap was 99.5%. The rate of complications was 12.0% and laparoscopy-associated complications occurred in four cases (2.0%). The rate of a positive margin was 6.5%. Two cases (1.0%) had local recurrence during a median follow-up period of 90 months. In 24 patients (12.0%), the volume of the flap was insufficient. When applied to total reconstruction, volume insufficiency occurred in 32.6% of patients. Cosmetic outcomes were mostly satisfactory. Approximately 80% of patients were rated as good or excellent by evaluation using a 4-point scale and Breast Cancer Conservative Treatment cosmetic results (BCCT.core) software. Donor-site scars were negligible, as in laparoscopic cholecystectomy. CONCLUSIONS: The LHOF has minimal donor-site morbidity and deformity, and oncological safety is promising. There is a limit to the adaptable volume, but the LHOF is an attractive option in partial breast reconstruction after BCS.

A new scarless oncoplastic breast-conserving surgery: modified round block technique.

Round block technique (RBT) is often utilized in breast-conserving surgery, but has problems of late-onset scar widening and changes in the shape or the position of the areola. We have modified RBT (MRBT) to resolve those problems. A circumferential incision was made without excision of the periareolar skin, and subcutaneous dissection was extended to the entire breast. The wound could be widened and moved onto the distant tumor by application of a wound retractor. Partial mastectomy was then performed under direct vision. The wound was easily closed without tension. Forty breast cancer patients were treated with MRBT. The median distance between the nipple and the tumor was 5.2 cm, and the median areolar size was 2.8 cm. Cosmetic results were satisfactory with minimal scar formation. There were neither subsequent changes in the shape nor the position of the areola. MRBT is a useful oncoplastic technique in patients with small areolae, and/or when the tumor location is distant from the nipple.