Bone metastases incidence and its correlation with hormonal and human epidermal growth factor receptor 2 neu receptors in breast cancer

Pareek, Ananya; Singh, Onkar; Yogi, Veenita; Ghori, Hameeduzzafar; Tiwari, Vivek; Redhu, Pallavi

doi:10.4103/jcrt.jcrt_235_18

Cited by 8 publications

(6 citation statements)

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“…This is consistent with a study of breast tissue samples analysed at Muhimbili National Hospital in Dar es Salaam in 2013 where the mean age was 48.3 years (Mwakigonja et al, 2017). Although in the West, breast cancer is typically a disease of older women, younger ages at presentation of MBC have been documented in several non-white populations such as in India (47 years) and Uganda (45 years) (Pareek et al, 2019;Nabawanuka et al, 2013).…”

Section: Discussionsupporting

confidence: 83%

“…The hormone receptor status of MBC is strongly related to the metastatic pattern. Hormone-receptor-positive (estrogen receptor [ER] and progesterone receptor [PR]) tumors are more likely to spread to bones as their primary site of metastases and have better survival outcomes; whereas hormone receptor-negative or human epidermal growth factor receptor 2 (HER2neu) positive tumors tend to develop as visceral metastasis (Pareek et al, 2019;Hou et al, 2021;Tao et al, 2016). Current recommendations for treating metastatic disease involve the use of first-line hormonal therapy for ER and PR-positive tumors.…”

Section: Introductionmentioning

confidence: 99%

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Metastatic patterns and hormone receptor status among breast cancer patients in Tanzania

Dharsee,

Haule,

Tarimo

2024

Tanzania J Hlth Res

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Introduction: Metastatic breast cancer is a common presentation in Tanzania. Estrogen-receptor (ER)-positive tumors are known to metastasize to the bones and require hormonal treatment as first-line therapy. Challenges with accessing immunohistochemistry services can delay information on breast cancer subtypes, further delaying treatment with effective hormonal therapy. Objectives: This study aimed to assess the pattern of distribution of metastatic lesions in patients with metastatic breast cancer and evaluate its association with their hormone and HER-2 status, which could help provide recommendations on the use of front-line hormone therapy in areas where access to immunohistochemistry is a challenge. Methods: A retrospective study covering histologically confirmed breast cancer patients in 2020 with metastatic lesions and complete medical records at Ocean Road Cancer Institute. Clinical information on the number, state and sites of metastasis, presence of symptoms and treatment received, and pathological variables, including histology, ER, PR and HER-2 status, were documented. Results: Forty-nine (96.1%) of 51 patients analysed were female, with a mean age of 49.5 years. 47% presented with up-front metastatic disease. Lung was the most common metastatic site (76.5%) followed by bone/spine (53%). About half the patients had multiple sites involved. ER-positive tumors accounted for 47%, PR positive for 31% and HER-2 positive 39.2%. ER-positive tumors were more likely to present as a recurrence than up-front metastasis. ER-positive tumors were significantly more likely to be associated with bone and spine metastasis (59%) compared to ER-negative tumors (29%) Conclusion: The clinical and pathological features of MBC in Tanzanian women are similar in many ways to those in other African regions. However, the ER positivity rate is lower. This study found a significant association between ER-positive tumours and skeletal metastasis, which has implications for the up-front treatment of these patients, especially where access to immunohistochemistry can be a challenge.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Metastatic patterns and hormone receptor status among breast cancer patients in Tanzania

Dharsee,

Haule,

Tarimo

2024

Tanzania J Hlth Res

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“…Once bone metastases occur, treatment with bisphosphonates or denosumab remain the only option in this incurable stage. Hormone receptor and HER2 positive breast cancer shows a higher incidence of bone metastases, but triple negative breast cancer patients with bone metastases exhibit a lower median survival [6,7]. Furthermore, triple negative breast cancer lacks an approach for targeted therapy.…”

Section: A B Rank Ctgfmentioning

confidence: 99%

“…The triple negative breast cancer (TNBC) subtype is defined as hormone receptor and HER negative and exhibits a particularly high invasiveness [5]. Although bone metastases are more likely to occur in hormone receptor or HER2 positive breast cancer subtypes, patients with bone metastases of TNBC show the shortest median survival among all breast cancer subtypes [6,7]. As a consequence, inhibitors targeting altered cellular signal transduction in bone metastases are the subject of current research [8].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of AKT3 Activates HER2 and DDR Kinases in Bone-Seeking Breast Cancer Cells, Promotes Metastasis In Vivo and Attenuates the TGFβ/CTGF Axis

Hinz

Baranowsky

Horn

et al. 2021

Cells

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Bone metastases frequently occur in breast cancer patients and lack appropriate treatment options. Hence, understanding the molecular mechanisms involved in the multistep process of breast cancer bone metastasis and tumor-induced osteolysis is of paramount interest. The serine/threonine kinase AKT plays a crucial role in breast cancer bone metastasis but the effect of individual AKT isoforms remains unclear. Therefore, AKT isoform-specific knockdowns were generated on the bone-seeking MDA-MB-231 BO subline and the effect on proliferation, migration, invasion, and chemotaxis was analyzed by live-cell imaging. Kinome profiling and Western blot analysis of the TGFβ/CTGF axis were conducted and metastasis was evaluated by intracardiac inoculation of tumor cells into NOD scid gamma (NSG) mice. MDA-MB-231 BO cells exhibited an elevated AKT3 kinase activity in vitro and responded to combined treatment with AKT- and mTOR-inhibitors. Knockdown of AKT3 significantly increased migration, invasion, and chemotaxis in vitro and metastasis to bone but did not significantly enhance osteolysis. Furthermore, knockdown of AKT3 increased the activity and phosphorylation of pro-metastatic HER2 and DDR1/2 but lowered protein levels of CTGF after TGFβ-stimulation, an axis involved in tumor-induced osteolysis. We demonstrated that AKT3 plays a crucial role in bone-seeking breast cancer cells by promoting metastatic potential without facilitating tumor-induced osteolysis.

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“…This evidence seems to suggest that Src nuclear localization is associated to lower aggressiveness in cancer. Interestingly, the aforementioned works (the only two cases in the literature providing the prognostic relevance for Src subcellular localization) refer to osteosarcoma and estrogen receptor-positive breast cancer, being the former a bone tumor and the latter a cancer with high tropism to bone as its primary site of metastases [88].…”

Section: Prognostic Roles Of Nuclear Srcmentioning

confidence: 99%

Nuclear Functions of the Tyrosine Kinase Src

Bagnato

Leopizzi²,

Urciuoli

et al. 2020

IJMS

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Src is the representative member of the Src-family kinases (SFKs), a group of tyrosine kinases involved in several cellular processes. Its main function has been for long confined to the plasma membrane/cytoplasm compartment, being a myristoylated protein anchored to the cell membrane and functioning downstream to receptors, most of them lacking intrinsic kinase activity. In the last decades, new roles for some SFKs have been described in the nuclear compartment, suggesting that these proteins can also be involved in directly regulating gene transcription or nucleoskeleton architecture. In this review, we focused on those nuclear functions specifically attributable to Src, by considering its function as both tyrosine kinase and adapting molecule. In particular, we addressed the Src involvement in physiological as well as in pathological conditions, especially in tumors.

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Bone metastases incidence and its correlation with hormonal and human epidermal growth factor receptor 2 neu receptors in breast cancer

Cited by 8 publications

References 0 publications

Metastatic patterns and hormone receptor status among breast cancer patients in Tanzania

Metastatic patterns and hormone receptor status among breast cancer patients in Tanzania

Knockdown of AKT3 Activates HER2 and DDR Kinases in Bone-Seeking Breast Cancer Cells, Promotes Metastasis In Vivo and Attenuates the TGFβ/CTGF Axis

Nuclear Functions of the Tyrosine Kinase Src

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