Effectiveness and tasks of breast MRI surveillance for high-risk women with cancer susceptibility genes other than BRCA1/2: a single institution study.

BACKGROUND: In Japan, with the introduction of multigene panel testing, there is an urgent need to build a new medical system for hereditary breast cancer patients that covers pathogenic variants other than BRCA1/2. The aim of this study was to reveal the current status of breast MRI surveillance for high-risk breast cancer susceptibility genes other than BRCA1/2 and the characteristics of detected breast cancer. METHODS: We retrospectively examined 42 breast MRI surveillance with contrast performed on patients with hereditary tumors other than BRCA1/2 pathogenic variants at our hospital from 2017 to 2021. MRI exams were evaluated independently by two radiologists. Final histopathological diagnosis for malignant lesions were obtained from surgical specimen. RESULTS: A total of 16 patients included TP53, CDH1, PALB2, ATM pathogenic variants and 3 variant of unknown significance. 2 patients with TP53 pathogenic variants were detected breast cancer by annual MRI surveillance. The rate of cancer detection was 12.5% (2/16). One patient was detected synchronous bilateral breast cancer and unilateral multiple breast cancers (3 lesions in 1 patient), so there were 4 malignant lesions in total. Surgical pathology of 4 lesions were 2 ductal carcinoma in situ, 1 invasive lobular carcinoma, and 1 invasive ductal carcinoma. MRI findings of 4 malignant lesions were detected as 2 non mass enhancement, 1 focus and 1 small mass. All of 2 patients with PALB2 pathogenic variants had previously developed breast cancer. CONCLUSIONS: Germline TP53 and PALB2 were strongly associated with breast cancer, suggesting that MRI surveillance is essential for breast cancer-related hereditary predisposition.

Giant cell tumor of soft tissue of the breast: Case report with H3F3A mutation analysis and review of the literature.

Giant cell tumors of soft tissue (GCT-ST) arising in the breast are extremely rare. We report a unique case of breast GCT-ST coincident with ductal carcinoma in situ (DCIS), diagnosed with histological, immunohistochemical, and H3F3A (Histone H3.3) mutation analyses. A 59-year-old woman preoperatively diagnosed with DCIS underwent total mastectomy for a cystic mass. Histology revealed a tumor composed of mononuclear cells interspersed with numerous osteoclast-like giant cells, resembling giant cell tumor of bone (GCT-B), with apocrine DCIS in proximity to the tumor. The mononuclear and giant cells were immunoreactive for CD68 and negative for cytokeratins. Granulomatous diseases, carcinomas with giant cells, and giant cell-type sarcomas were excluded by histological and immunophenotypic features. Lack of H3F3A mutation eliminated the possibility of GCT-B metastasizing to the breast. These findings were consistent with GCT-ST of the breast. To our knowledge, this is the ninth reported case of breast GCT-ST, but the first case that accompanied DCIS or involved H3F3A mutation status investigation. For correct diagnosis of this rare tumor, it is important for pathologists to raise the possibility of GCT-ST when encountering giant cell-rich breast lesions and to exclude other differential diagnoses by combining the results of histological, immunohistochemical, and genetic analyses.

Usefulness of second-look ultrasonography using anatomical breast structures as indicators for magnetic resonance imaging-detected breast abnormalities.

BACKGROUND: Second-look ultrasonography (US) is commonly performed for breast lesions detected using magnetic resonance imaging (MRI), but the identification rate of these lesions remains low. We investigated if US methods using anatomical breast structures can improve the lesion identification rate of MR-detected lesions and evaluated the diagnostic performance of fine-needle aspiration cytology (FNAC) of the second-look US using the above-mentioned method. METHODS: We retrospectively assessed 235 breast lesions (hereinafter, "targets") subjected to second-look US following MRI between January 2013 and September 2015. US was employed using the conventional methods, and this assessment measured the positional relationships of lesions with regard to surrounding anatomical breast structures (glandular pattern, Cooper's ligaments, adipose morphology, and vascular routes). Associations were assessed among the following variables: the MRI findings, target size, identification rate, and main US indicators that led to identifying the target; FNAC results and MRI findings; MRI findings and histopathological findings; and FNAC results and histopathological findings. Moreover, the sensitivity and specificity of FNAC were determined. RESULTS: The identification rate was 99%. The main US indicators leading to identification were a glandular pattern (28-30% of lesions) and other breast structures (~ 25% of lesions). FNAC was performed for 232 targets with the following results: sensitivity of 85.7%, specificity of 91.6%, PPV of 94.1%, NPV of 92.9%, false-negative rate of 14.3%, false-positive rate of 2.1%, and accuracy of 89.7%. CONCLUSIONS: Second-look US using anatomical breast structures as indicators and US-guided FNAC are useful for refining the diagnosis of suspicious breast lesions detected using MRI.

Five screening-detected breast cancer cases in initially disease-free BRCA1 or BRCA2 mutation carriers.

Individuals carrying pathogenic BRCA1 or BRCA2 mutations have an increased lifetime risk of breast and/or ovarian cancer. The incidence of breast cancer amongst disease-free BRCA mutation carriers under surveillance and the clinical and pathological characteristics of those who subsequently develop the disease remain unclear in Japan. We reviewed the records of 155 individuals with BRCA1 or BRCA2 mutations identified by genetic testing between January 2000 and December 2016. At the time of genetic testing, 26 individuals with one of these mutations had no history of breast cancer and were therefore enrolled in a surveillance program that included biannual ultrasonography, clinical breast examination, annual mammography, and conditional magnetic resonance imaging for the early detection of primary breast cancer. During the surveillance period, 5 individuals with BRCA1 or BRCA2 mutations were diagnosed with primary breast cancer. The mean surveillance duration until breast cancer diagnosis was 48 months. The incidence of primary breast cancer during surveillance in initially disease-free BRCA mutation carriers was 4.23%/year. In two cases, the tumors were only detectable on MRI. The case 5 patient who presented with a tumor that was detected by self-examination, which then grew rapidly, had stage IIB triple-negative breast cancer. In conclusion, our results show that some challenges exist in the early detection of breast cancers in BRCA1 or BRCA2 mutation carriers. There are also some difficulties in approaching those individuals in Japanese society.

A diagnostic strategy for breast calcifications based on a long-term follow-up of 615 lesions.

PURPOSE: To clarify the long-term outcomes of breast calcifications after stereotactic vacuum-assisted breast biopsy (SVAB) and to develop strategy after SVAB. METHODS: Subject comprised 594 patients with 615 calcifications who underwent SVAB. 371 (60.3%) lesions were diagnosed as benign, 38 (6.2%) as indeterminate, and 206 (33.5%) as malignant. We retrospectively reviewed post-biopsy courses of non-malignant lesions which were followed. A histopathological review was performed for false negatives to clarify the reasons. RESULTS: Of the 308 patients with benign lesions, with a median follow-up time of 55.8 months, re-biopsy was performed for 11 (3.6%) due to changes of imaging, and 4 (1.3%) were diagnosed as breast cancer. Of the 36 patients with indeterminate lesion, re-biopsy was performed for 16 (44.4%), and 8 (22.2%) were diagnosed as breast cancer, while 20 (55.6%) showed no changes in imaging with a median follow-up time of 91.7 months without re-biopsy. Weak atypism of intraductal carcinoma may cause a false-negative diagnosis in SVAB for breast calcifications. CONCLUSIONS: When SVAB results in non-malignant, patients may be followed by annual screening, while re-biopsy needs to be performed for the patients with a discordant result of SVAB and with changes in an imaging finding during a follow-up.

Pattern of Tumor Shrinkage during Neoadjuvant Chemotherapy Is Associated with Prognosis in Low-Grade Luminal Early Breast Cancer.

Purpose To evaluate the association between tumor shrinkage patterns shown with magnetic resonance (MR) imaging during neoadjuvant chemotherapy (NAC) and prognosis in patients with low-grade luminal breast cancer. Materials and Methods This retrospective study was approved by the institutional review board and informed consent was obtained from all subjects. The low-grade luminal breast cancer was defined as hormone receptor-positive and human epidermal growth factor receptor 2-negative with nuclear grades 1 or 2. The patterns of tumor shrinkage as revealed at MR imaging were categorized into two types: concentric shrinkage (CS) and non-CS. Among 854 patients who had received NAC in a single institution from January 2000 to December 2009, 183 patients with low-grade luminal breast cancer were retrospectively evaluated for the development set. Another data set from 292 patients who had received NAC in the same institution between January 2010 and December 2012 was used for the validation set. Among these 292 patients, 121 patients with low-grade luminal breast cancer were retrospectively evaluated. Results In the development set, the median observation period was 67.9 months. Recurrence was observed in 31 patients, and 16 deaths were related to breast cancer. There were statistically significant differences in both the disease-free survival (DFS) and overall survival (OS) rates between patterns of tumor shrinkage (P < .001 and P < .001, respectively). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .001) and OS (P = .009) rate. In the validation set, the median follow-up period was 56.9 months. Recurrence was observed in 20 patients (16.5%) and eight (6.6%) deaths were related to breast cancer. DFS rate was significantly longer in patients with the CS pattern (72.8 months; 95% confidence interval [CI]: 69.9, 75.6 months) than in those with the non-CS pattern (56.0 months; 95% CI: 49.1, 62.9 months; P ≤ .001). The CS pattern was associated with an excellent prognosis (median OS, 80.6 months; 95% CI: 79.3, 81.8 months vs 65.0 months; 95% CI: 60.1, 69.8 months; P = .004). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .007) and OS (P = .037) rates. Conclusion The CS pattern as revealed at MR imaging during NAC had the only significant independent association with prognosis in patients with low-grade luminal breast cancer. © RSNA, 2017.

Bone metastases from breast cancer: associations between morphologic CT patterns and glycolytic activity on PET and bone scintigraphy as well as explorative search for influential factors.

BACKGROUND: This study aimed to compare the detection of bone metastases from breast cancer on F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and bone scintigraphy (BS). An explorative search for factors influencing the sensitivity or uptake of BS and FDG-PET was also performed. METHODS: Eighty-eight patients with bone metastases from breast cancer were eligible for this study. Histological confirmation of bone metastases was obtained in 31 patients. The bone metastases were visually classified into four types based on their computed tomography (CT) appearance: osteoblastic, osteolytic, mixed, and negative. The sensitivity of BS and FDG-PET were obtained regarding CT type, adjuvant therapy, and the primary tumor characteristics. The FDG maximum standardized uptake value (SUVmax) was analyzed. RESULTS: The sensitivities of the three modalities (CT, BS, and FDG-PET) were 77, 89, and 94%, respectively. The sensitivity of FDG-PET for the osteoblastic type (69%) was significantly lower than that for the other types (P < 0.001), and the sensitivity of BS for the negative type (70%) was significantly lower than that for the others. Regarding tumor characteristics, the sensitivity of FDG-PET significantly differed between nuclear grade (NG)1 and NG2-3 (P = 0.032). The SUVmax of the osteoblastic type was significantly lower than that of the other types (P = 0.009). The SUVmax of NG1 was also significantly lower than that of NG2-3 (P = 0.011). No significant difference in FDG uptake (SUVmax) was detected between different histological types. CONCLUSION: Although FDG-PET is superior to BS for the detection of bone metastases from breast cancer, this technique has limitations in depicting osteoblastic bone metastases and NG1.

Surgical excision without whole breast irradiation for complete resection of ductal carcinoma in situ identified using strict, unified criteria.

BACKGROUND: The definition of complete resection of ductal carcinoma in situ (DCIS) is difficult to standardize because of the high variety of surgical breast conserving procedures, specimen handling, and pathological examinations. Using strictly controlled criteria in a single institute, the present study aimed to determine the ipsilateral breast cancer rate when radiotherapy is omitted following complete resection of DCIS. METHODS: We retrospectively examined 363 consecutive DCIS patients who underwent breast-conserving surgery, and of these, 125 (34.4%) had complete resection according to the criteria. We finally included 103 patients who omitted radiotherapy. Ipsilateral and contralateral breast cancer events were assessed. RESULTS: The median follow-up period was 118 months. The incidences of ipsilateral and contralateral breast cancer and ipsilateral invasive breast cancer at 10 years were 10.8%, 9.1%, and 3.6%, respectively. No patient died of breast cancer. CONCLUSION: If complete resection of DCIS can be ensured, the annual incidence of ipsilateral breast cancer, even without irradiation, can be limited to approximately 1%, which equals the incidence of contralateral breast cancer.

Accuracy of magnetic resonance imaging for predicting pathological complete response of breast cancer after neoadjuvant chemotherapy: association with breast cancer subtype.

A pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is a signature of favorable prognosis in breast cancer. The aim of this study was to assess the accuracy of magnetic resonance imaging (MRI) in predicting the pCR after NAC. 265 women with stage II or III breast cancer who underwent surgery after NAC were retrospectively investigated for MRI findings before and after the NAC. Correlation of pCR with an "imaging complete response" (iCR), defined as no detectable tumor on all serial images with dynamic contrast-enhanced T1-weighted imaging, was evaluated with respect to each tumor subtype. Of 265 cases, 44 (16.6 %) and 24 (9.1 %) were diagnosed as iCR and pCR, respectively. Nineteen of the 44 iCR cases (43.2 %) were assessed as pCR, and 216 (97.7 %) of the 221 non-iCR cases were assessed as non-pCR. The accuracy (ACC), the pCR predictive value (PPV) and the non-pCR predictive value (NPV) were 88.7, 43.2, and 97.7 %, respectively. When assessed according to each tumor subtype, the ACC, PPV and NPV were 93.2, 21.4 and 100 % for luminal subtype, 70.8, 0 and 89.5 % for luminal/HER2 subtype, 75, 57.1 and 88.8 % for HER2-enriched subtype, and 90.9, 72.7 and 97 % for triple-negative subtype, respectively. MRI is a valuable modality for predicting pCR of breast cancer after NAC treatment. However, its accuracy varies greatly in different breast cancer subtypes. Whereas MRI closely predicts pCR in the triple-negative subtype, iCR in the luminal subtype is often an over-estimation. On the other hand, residual lesions identified by MRI are reliable markers of non-pCR for the luminal subtype.

Mammary ductoscopy and watchful follow-up substitute microdochectomy in patients with bloody nipple discharge.

PURPOSE: In order to evaluate the diagnostic and therapeutic potential of mammary ductoscopy and watchful follow-up for treating bloody nipple discharge, we investigated the incidence of cancer evolving from the location related to the affected duct and the disappearance of nipple discharge. PATIENTS AND METHODS: Between April 1998 and March 2008, we assessed 709 lesions among 624 patients without a diagnosis of malignancy at the time of 6 months after mammary ductoscopy. The median follow-up time was 5.5 years. We reviewed the subjects' charts retrospectively and investigated the dates on which discharge-related cancer was diagnosed and the disappearance of discharge was noted after the initial examination with mammary ductoscopy. RESULTS: The incidence of cancer evolving from the location related to the pathological duct was 11 % (78/709). Nipple discharge disappeared in 480 (85.1 %) of the 564 followed up lesions, with the exception of 78 breast cancers and 67 resected benign lesions. The rate of disappearance for nipple discharge in the cases of intraductal papilloma at the first examination was 82.5 %. In cases in which no obvious lesions were observed on mammary ductoscopy, there was a 90 % probability that the nipple discharge would disappear, and the rate of evolving breast cancer in the cases of atypical papillary lesions at the first examination was significantly higher than that observed in the cases of intraductal papilloma, at 50 and 8.9 %, respectively. CONCLUSIONS: Information revealed by mammary ductoscopy is useful for differentiating patients who should be subjected to intensive examinations and those who should expect disappearance of their discharge. Mammary ductoscopy and watchful follow-up can substitute microdochectomy in patients with bloody nipple discharge.

Decreased hormonal sensitivity after childbirth rather than the tumor size influences the prognosis of very young breast cancer patients.

PURPOSE: There is a significant difference in the mean tumor size between very young breast cancer patients and their elder counterparts. A simple comparison may show obvious prognostic differences. We investigated the prognostic impact of age by reducing the influence of the tumor size, which is thought to be a confounding factor. PATIENTS AND METHODS: We investigated 1,880 consecutive pT1-4N0-3M0 breast cancer patients treated at less than 45 years of age between 1986 and 2002 and conducted a case-control study of breast cancer subjects less than 30 years of age. Each patient (Younger than 30) was matched with a corresponding control subject (Elder counterpart) based on an age 15 years above the patient's age, a similar tumor size and a status of being within 1 year after surgery. In addition, we assessed 47 patients with pregnancy-associated breast cancer (PABC). The levels of hormone receptors were measured using an enzyme immunoassay (EIA), and receptor-positive cases were divided into "weakly" and "strongly" positive groups based on the median value. Years from the last childbirth (YFLC) was categorized as "recent" and "past" at the time point of 8 years. RESULTS: There were fewer past YFLC cases, more partial mastectomy cases, a higher rate of scirrhous carcinoma or solid-tubular carcinoma in the Younger than 30 group than in the Elder counterpart group. The rates of a PgR-negative status in the Younger than 30 and Elder counterpart groups were 45.1 and 29.9%, respectively, As for the relationship between the PgR-negative rate and YFLC, the rates of a PgR-negative status in the past YFLC, nulliparous, recent YFLC and PABC groups were 31.9, 37.7, 44.4 and 65.7%, respectively. On the other hand, the rates of strongly positive cases were 42.6, 30.2, 22.2 and 8.6%, respectively. The 10-year recurrence-free survival rates in the Younger than 30, Elder counterpart and PABC groups were 61.7, 65.6 and 54.1%, respectively. The differences between the groups were not significant. In a multivariate analysis, independent prognostic facers included the number of lymph node metastases (4-9, HR:3.388, 95% CI 1.363-8.425, p = 0.0086, over 10, HR: 6.714, 2.033-22.177, p = 0.0018), solid-tubular carcinoma (HR 3.348, 1.352-8.292, p = 0.0090), scirrhous carcinoma (HR 2.294, 1.013-5.197, p = 0.0465) and past YFLC (HR 0.422, 0.186-0.956, p = 0.0387). An age younger than 30 was not found to be an independent prognostic factor. CONCLUSIONS: The prognosis of the very young women was the same as their elder counterparts with a matched tumor size, and age was not identified to be an independent prognostic factor according to the multivariate analysis. Recent childbirth probably influences the prognosis of patients younger than 30 years of age with breast cancer by lowering hormonal sensitivity.

Clear cell sarcoma of the neck which metastasized to the mammary gland.

Malignant neoplasms very rarely metastasize to the mammary gland, the incidence of which is reported as 0.5-2%. Clear cell sarcoma is a rare neoplasm, accounting for approximately 1% of all soft tissue tumors, which commonly occurs in the distal extremities of young adults aged approximately 20 to 40 years. So it is also called malignant melanoma of soft parts because it frequently produces melanin. We report a case of a 26-year-old woman who presented with a neck mass. The mass was surgically removed, and pathological diagnosis was clear cell sarcoma of the neck, harboring the EWS-ATF1 chimeric gene. Computed tomography detected a right breast mass 11 months after operation. She was referred to our department, and the right breast tumor was resected. Histopathological examination revealed a 2.5-cm, well-defined mass composed of nests of small, spindle-shaped tumor cells with abundant, clear cytoplasm containing round nuclei and prominent nucleoli. The tumor cells were immunohistochemically positive for HMB45, S-100, and Melan-A. These findings led to a diagnosis of metastasis of clear cell sarcoma to the mammary gland. This is the first report of clear cell sarcoma of the neck which metastasized to the mammary gland.

Breast cancer associated with mammary hamartoma.

Mammary hamartoma is an infrequent, nonmalignant lesion. Only 12 cases of carcinomas associated with a hamartoma have been previously documented in the literature. We describe a case of invasive ductal carcinoma arising in the mammary hamartoma during the follow-up period of a previously diagnosed hamartoma.

Influence of lymphatic invasion on locoregional recurrence following mastectomy: indication for postmastectomy radiotherapy for breast cancer patients with one to three positive nodes.

PURPOSE: The indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status. METHODS AND MATERIALS: Retrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and ly status. RESULTS: Multivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p < 0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p < 0.001 vs. p = 0.295). CONCLUSION: Among postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT.

Parametrial involvement in FIGO stage IB1 cervical carcinoma diagnostic impact of tumor diameter in preoperative magnetic resonance imaging.

BACKGROUND: In the surgical treatment for early-stage cervical carcinoma, it is important to identify preoperatively a low-risk group of patients as candidates for less radical surgery to avoid the morbidity associated with radical hysterectomy. The aim of this study was to evaluate the correlation between tumor diameter measured preoperatively using magnetic resonance imaging (MRI) and pathological prognostic factors in International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical carcinoma. METHODS: A total of 125 patients with FIGO stage IB1 cervical cancer were included in this study. Clinical records, pathology reports, and MRI findings were retrospectively reviewed. RESULTS: Histological diagnosis was squamous cell carcinoma in 57 patients and non squamous cell carcinoma in 68 patients. All patients underwent preoperative evaluation by MRI within a median period of 13.5 days before surgery. The tumor diameter measured by MRI ranged from zero (no tumor detected) to 42 mm, with a median of 23 mm.Pathological prognostic factors included parametrial involvement, lymph node metastasis,deep stromal invasion, and lymphovascular space invasion. All these factors were found less frequently in patients with a smaller tumor diameter. Most notably, parametrial involvement was seen in none of the patients with tumors 20 mm or less and was detected only in patients with tumors greater than 20 mm (P = 0.01). CONCLUSIONS: In the FIGO stage IB1 cervical carcinoma, the tumor diameter measured preoperatively by MRI correlates well with other pathological prognostic factors, especially with parametrial involvement. This finding suggests that the tumor diameter measured in preoperative MRI may serve as a strong predictor of parametrial involvement in FIGO stage IB1 cervical carcinoma, which can be used to select a candidate population for less radical surgery without the need for a cone biopsy before hysterectomy.

Invasive carcinoma of the breast accompanied by coarse calcification.

OBJECTIVE: We describe the case of a woman with a left breast mass. At mammography, the mass was shown to be irregular and accompanied by coarse calcification. Core needle biopsy revealed invasive carcinoma and a mastectomy was performed. Histopathology showed fibrosis with partial hyalinization eccentrically placed within the tumor with a large area of calcification at the core. CONCLUSION: Benign calcifications within a breast mass are not diagnostic of a benign process if the imaging characteristics of the mass are suspicious.

Malignant mucosal melanoma of the eustachian tube.

Malignant mucosal melanoma is a rare condition. Although the head and neck region is the most common site for mucosal melanoma, a melanoma arising in the eustachian tube is rare. Here we present a case of mucosal melanoma arising in the right eustachian tube.