Concurrent trastuzumab deruxtecan-induced interstitial lung disease and COVID-19 in the treatment of advanced breast cancer.

Patients with cancer are at an increased risk of developing coronavirus disease 2019 (COVID-19) infection. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) against epidermal growth factor receptor 2 (HER2)-positive cancer, known to cause drug-induced interstitial lung disease (DILD), including drug-induced pneumonitis. A 60-year-old woman with breast cancer developed a fever during treatment with T-DXd and was diagnosed with COVID-19. The fever persisted for approximately 3 weeks, and chest computed tomography showed multiple consolidations with bilateral peripheral predominance. Since the clinical course was atypical for COVID-19 due to the long duration of the fever and the CT pattern was frequently seen in T-DXd-induced ILD, the patient was diagnosed with T-DXd-induced ILD, following which, prednisolone was started, leading to improvement in the symptoms and fading of shadows. Even in patients suspected of COVID-19 pneumonia, physicians should consider the possibility of DILD, particularly in patients undergoing cancer treatment.

Everolimus for Treating Hormone Receptor-positive Metastatic Breast Cancer Previously Treated With Cyclin-dependent Kinase 4/6 Inhibitors.

BACKGROUND/AIM: Cyclin-dependent kinase (CDK) 4/6 inhibitors have become the standard of care as the first- and second-line treatments for hormone receptor-positive (HR+) or human epidermal growth factor receptor 2 (HER2)-negative metastatic and recurrent breast cancers. Although CDK 4/6 inhibitors can markedly prolong progression-free survival, there is no clear evidence of their post-treatment effects. The option of developing mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, has been discussed as a post-treatment option for such patients. This study aimed at determining everolimus' efficacy as a post-treatment option following CDK4/6 inhibitor administration in clinical settings. PATIENTS AND METHODS: Thirteen patients who received everolimus as a post-treatment after CDK4/6 inhibitor therapy from December 2017 to July 2021 were retrospectively reviewed. The primary endpoint was progression-free survival; the secondary endpoints were overall response rate, clinical benefit rate, and overall survival. RESULTS: The median patient age, progression-free survival, and overall survival were 59 years (range=44-76 years), 9.1 months (95% confidence interval=2.3 to not reached), and 37.4 months (95% confidence interval=12.3-37.4), respectively. The overall response rate and clinical benefit rate were 15.3% (2/13) and 46.2% (6/13), respectively. CONCLUSION: Considering there is a mechanism of resistance to CDK4/6 inhibitors, everolimus would be important as an effective post-treatment for HR+ or HER2-negative metastatic and recurrent breast cancers treated with CDK4/6 inhibitors in clinical settings.

Infiltration of CD4, CD8, CD56, and Fox-P3-positive lymphocytes in breast carcinoma tissue after neoadjuvant chemotherapy with or without trastuzumab.

BACKGROUND: Trastuzumab (Tz) is assumed to prime antibody-dependent cellular cytotoxicity (ADCC); however, it remains unclear whether Tz therapy can clinically induce adaptive cellular immunity. OBJECTIVE: Adaptive Cellular Immune Effect of Tz Therapy. METHODS: This study included 29 surgical invasive breast carcinomas administered neoadjuvant chemotherapy with Tz (15 cases) or without Tz (14 cases). The numbers of immunoreactive cells (CD4, CD8, CD56, and Fox-P3) in three different compartments (intratumoral, adjacent stromal, and distant stromal) were determined. RESULTS: The average number of adjacent stromal CD4-positive, CD8-positive, and Fox-P3-positive cells in the Tz+ group was significantly greater than that in the Tz- group (p = 0.036, 0.0049, and 0.043, respectively). However, the number of Fox-P3-positive cells was much less than that of CD4-positive cells. Moreover, distant stromal CD4-positive and CD8-positive cells in the Tz+ group was also significantly greater than that of the Tz- group (p = 0.029 and 0.032, respectively). Only a small number of CD56-positive natural killer cells, playing a main role in ADCC, accumulated at the tumor site after Tz therapy. CONCLUSIONS: The results suggest that Tz therapy induces adaptive cellular immunity, including infiltration of both CD4-positive helper T cells and CD8-positive cytotoxic T cells into the breast carcinoma lesion.

Immunohistochemical analyses of CD44 variant isoforms in invasive micropapillary carcinoma of the breast: comparison with a concurrent conventional invasive carcinoma of no special type component.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a distinct histopathological variant of breast carcinoma and frequently develops lymph node metastases. CD44 is a family of transmembrane glycoprotein receptors with multiple variant isoforms (CD44v), which have tissue-specific expression. Previous studies have demonstrated a loss or gain of CD44v and CD44 standard form (CD44s) expression in breast carcinomas. In this study, we analyzed the immunoprofiles of CD44s, CD44v6, and CD44v9 in IMPC and compared them with those in a concurrent invasive carcinoma of no special type (ICNST) component, thus clarifying the significance of CD44 expression in IMPC. METHODS: Twenty-one consecutive cases of mixed IMPC were included in this study. The expression statuses of CD44s, CD44v6, and CD44v9 in both the IMPC and ICNST components were analyzed semiquantitatively by immunohistochemistry. RESULTS: The immunohistochemical scores of CD44s, CD44v6, and CD44v9 were significantly decreased in the IMPC component compared to the ICNST component (p = 0.00335 for CD44s, p = 0.000982 for CD44v6, and p = 0.00271 for CD44v9). Moreover, the immunohistochemical scores of CD44v6 in the IMPC component and CD44v9 in the ICNST component of lymph node metastasis cases were significantly lower compared to cases without lymph node metastasis (p < 0.01). CONCLUSIONS: Decreased CD44 expression may play an important role in promoting lymph node metastasis in IMPC through an inability or decreased capacity to bind with the surrounding stroma. Moreover, high CD44s+ expression levels in the concurrent ICNST component may be related to the development of IMPC.

Giant cell arteritis of the breast: a case report with a review of literatures.

Although giant cell arteritis (GCA), clinically designated as temporal arteritis, is recognized as a systemic disease, the breast may be the primary organ in which it is manifested. GCA of the breast is a rare disease that mainly occurs in postmenoposal elderly women. It manifests as nodules or pain in the breast, with or without tenderness, and is associated with significant constitutional symptoms that resemble those of polymyalgia rheumatica (PMR). These symptoms can be treated with or without prednisone therapy and can improve without the development of organ dysfunction. The clinical manifestations can often be recognized only by retrospective analysis after excisional biopsy. GCA of the breast occasionally mimics carcinoma, and its initial manifestations may be similar to those of other forms of vasculitis involving the breast, such as polyarteritis nodosa and Wegener granulomatosis. Biopsy is indispensable for establishing a definitive diagnosis. Thus far, the findings of imaging procedures, such as mammography and ultrasonography, for patients with mammary GCA have not been reported in detail, and no distinctive findings associated with this condition have been identified. Considering this and the fact that spontaneous remission may occur in some cases, mammary GCA probably often goes undiagnosed or may be misdiagnosed as an ordinary mammary disease. GCA of the breast should be considered as a potential diagnosis in the case of elderly women presenting with PMR-like symptoms and tenderness, lumps, or pain in the breast. We report a case of GCA affecting the breast and review previous reports on this condition in an attempt to summarize the features that distinguish this disease from other vascular diseases of the breast.