Germline variant of BRCA1 c.5332G>A has clinical features of hereditary breast and ovarian cancer syndrome.

The proband was a 39-year-old Japanese woman with stage I triple negative breast cancer. Germline BRCA1 and BRCA2 genetic testing revealed the presence of a BRCA1 c.5332G>A (p.Asp1778Asn) variant classified as a VUS in the heterozygous state. She underwent curative surgery and adjuvant chemotherapy for her TNBC, but no intensive follow-up or risk-reducing surgery was performed in contrast to normal practice in a patient with hereditary breast and ovarian cancer syndrome. At postoperative 2 years 6 months, elevation of CA15-3 led to the diagnosis of Stage III high-grade serous ovarian cancer. Studies and information in public databases at the time of the patient's genetic testing showed only VUS results for c.5332G>A; within the next few years, one pathogenic and one likely pathogenic result were confirmed. Thus, according to a joint consensus recommendation of the ACMG/AMP, c.5332G>A is considered 'likely pathogenic'. The public database should be checked regularly for VUS results, and practical management should be considered if reliable likely pathogenic or pathogenic reports were added.

Short- and long-term outcomes of immediate breast reconstruction surgery after neoadjuvant chemotherapy.

PURPOSE: Immediate breast reconstruction (IBR) is a standard option for breast cancer patients, although its utility in patients with advanced breast cancer requiring neoadjuvant chemotherapy (NAC) is debatable. We assessed the short-term complications and long-term prognosis of IBR after NAC. METHODS: We retrospectively analyzed 1135 patients with IBR and/or NAC between 2010 and 2018, 43 of whom underwent IBR after NAC. RESULTS: Twenty-five patients underwent reconstruction with a tissue expander (TE) followed by silicon breast implantation, 5 with a latissimus dorsi muscle transfer flap, and 13 with a deep inferior epigastric perforator flap. Complete surgical resection with a free margin confirmed by a pathological assessment was achieved in all patients. The evaluation of the short-term complications indicated no cases of total flap necrosis, two cases of partial flap necrosis, and one case of wound infection. Only one case required postponement of subsequent therapy due to partial flap necrosis. A long-term evaluation indicated no local recurrence, although distant metastasis was observed in 4 cases, 3 patients died, and TE removal after post-mastectomy radiotherapy (PMRT) was performed in 2 of 11 TE cases. CONCLUSION: IBR may be a viable option in patients with advanced breast cancer who achieve complete surgical resection after NAC.

Metastasis of breast cancer to liver through direct lymphatic drainage: a case report.

Breast cancer liver metastasis (BCLM) is considered to occur by hematogenous spread of primary breast cancer cells. We herein present a case of lymphatic BCLM that was confirmed by preoperative imaging for sentinel lymph node biopsy (SLNB). A woman in her early 70s was diagnosed with clinical stage T2N0M0 invasive lobular cancer of the left breast. She underwent mastectomy with SLNB. Preoperative lymphoscintigraphy showed intense accumulation of isotope in the upper abdomen, corresponding to segment IV of the liver on single-photon emission computed tomography/computed tomography (SPECT/CT). However, no abnormalities were detected on magnetic resonance imaging. At 2.5 years postoperatively, the patient's serum CA15-3 concentration was elevated, and positron emission tomography/computed tomography (PET/CT) showed a solitary liver metastasis. The PET/CT findings were similar to the SPECT/CT findings obtained 2.5 years earlier, indicating that the BCLM had developed lymphatically. To the best of our knowledge, this is the first case report of lymphatic BCLM proven by imaging examination.

Safety and Effectiveness of Areola-sparing Mastectomy for Breast Cancer With Intraductal Lesions.

BACKGROUND/AIM: Areola-sparing mastectomy (ASM), a conservative mastectomy with nipple hollowing, can be applied to intraductal breast cancer with a tumour-nipple-areola complex (NAC) distance of ≤2 cm. Here, we evaluated the safety and effectiveness of ASM. PATIENTS AND METHODS: We retrospectively reviewed the surgical outcomes of 61 patients (64 breasts) who underwent ASM between 2016 and 2020. RESULTS: Of the 64 breasts, 33 (51.6%) underwent ASM because the tumour-NAC distance on preoperative magnetic resonance imaging was ≤2 cm. Two patients had positive excisional margins but these were at the posterior areola surface therefore additional resection was possible. Over a median postoperative observation period of 16 months (range=3-52 months), one patient developed chest wall recurrence that was resected and did not recur again. CONCLUSION: For breast cancer with an extensive intraductal component, ASM is a good alternative to nipple-sparing mastectomy because it allows safe resection while maintaining aesthetics.

[A Case Report on the Effectiveness of Olaparib in a Patient with Recurrent Breast Cancer with Human Immunodeficiency Virus Infection].

A 43 -year-old woman presented to the hospital with a right breast tumor. She had been treated for human immunodeficiency virus(HIV)infection for 5 years. After being diagnosed with right breast cancer, she underwent total mastectomy and sentinel lymph node biopsy, which indicated T2N1M0 triple-negative breast cancer. She received doxorubicin and cyclophosphamide( AC)followed by docetaxel(AC-T)as postoperative adjuvant chemotherapy. However, 14 months after the adjuvant chemotherapy finished, distant metastasis occurred in the brain, lung, and mediastinum lymph nodes. Treatment for relapse was initiated, with whole brain radiotherapy followed by paclitaxel plus bevacizumab combination therapy(PB); however, new metastatic lesions were found in the bone, liver, and mediastinum lymph node after 2 courses of PB. Given the risk of hereditary breast and ovarian cancer syndrome, a BRCAgene test was performed when the patient received radiotherapy for left recurrent laryngeal nerve paralysis caused by mediastinal lymph nodes; this showed a result positive for a deleterious mutation in BRCA1. Thus, treatment with olaparib, a poly(ADP-ribose)polymerase(PARP)inhibitor, was started. Metastatic lesions, including barky growth, in the liver metastasis were well controlled, as confirmed by CT imaging 4 months after the start of olaparib.

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.

Prognostic impact and possible pathogenesis of lymph node metastasis in ductal carcinoma in situ of the breast.

PURPOSE: Ductal carcinoma in situ (DCIS)-preinvasive breast cancer-with lymph node metastasis can clinically be treated as different stages: occult invasive cancer with true metastasis (T1N1) or pure DCIS with iatrogenic dissemination (TisN0). In this retrospective cohort study, we aimed to elucidate the prognostic impact and possible pathogenesis of nodal metastasis in DCIS to improve clinical management. METHODS: Subjects were comprised of 427 patients with routine postoperative diagnosis of DCIS who underwent sentinel node (SN) biopsy using molecular whole-lymph-node analysis. Clinicopathological characteristics and prognosis were compared between SN-positive and -negative patients. Primary tumour tissues of SN-positive patients were exhaustively step-sectioned to detect occult invasions, and predictive factors for occult invasion were investigated. Median follow-up time was 73.6 months. RESULTS: Of the 427 patients, 19 (4.4%) were SN-positive and 408 (95.6%) were SN-negative. More SN-positive patients received adjuvant systemic therapy than SN-negative patients (84.2% vs. 5.4%). Seven-year distant disease-free survivals were favourable for both cohorts (SN-positive, 100%; SN-negative, 99.7%). By examining 1421 slides, occult invasion was identified in 9 (47.4%) of the 19 SN-positive patients. Tumour burdens in SN and incidence of non-SN metastasis were similar between patients with and without occult invasion, and no predictive factor for occult invasion was found. CONCLUSIONS: Node-positive DCIS has favourable prognosis with adjuvant systemic therapy. Half of the cases may be occult invasive cancer with true metastasis. In practical settings, clinicians may have to treat these tumours as node-positive small invasive cancers because it is difficult to predict the pathogenesis without exhaustive primary tumour sectioning.

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.

A new molecular-based lymph node staging classification determines the prognosis of breast cancer patients.

BACKGROUND: The one-step nucleic acid amplification (OSNA) assay is a novel molecular method that can detect metastasis in a whole lymph node based on cytokeratin 19 mRNA copy number. This cohort study aimed to establish an OSNA-based nodal staging (pN(mol)) classification for breast cancer. METHODS: The cohort consisted of 1039 breast cancer patients who underwent sentinel node (SN) biopsy using the OSNA assay. Cutoff value of the SN tumour burden stratifying distant disease-free survival (DDFS) was determined, and predictive factors for DDFS and breast cancer-specific survival (BCSS) were investigated. pN(mol) classification of the SN status was defined as: pN0(mol)(sn), SN negative; pN1mi(mol)(sn), SN positive and tumour burden