Distinct Pattern of Metastases in Patients with Invasive Lobular Carcinoma of the Breast

Mathew, Aju; Rajagopal, Padma Sheila; Villgran, Vipin; Sandhu, Gurprataap S.; Jankowitz, Rachel C.; Jacob, Mini E.; Rosenzweig, Margaret; Oesterreich, Steffi; Brufsky, Adam

doi:10.1055/s-0043-109374

Cited by 87 publications

(72 citation statements)

References 24 publications

(36 reference statements)

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“…WNT4 is required for cell migration and ovary invasion in murine PTEN-null models of FTE-derived ovarian cancer [62], suggesting that WNT4 is critical in early ovarian tumorigenesis. Perhaps consistent with this role of WNT4 in migration/invasion, both OvCa and ILC metastasize to the abdomen/peritoneal cavity, ILC being unique among breast cancers in this regard [63,64]. Defining WNT4 signaling in these tumors may provide new insight in to targeting metastatic OvCa and ILC.…”

Section: Discussionmentioning

confidence: 79%

Estrogen controls mTOR signaling and mitochondrial function via WNT4 in lobular carcinoma cells

Shackleford

Bordeaux

et al. 2019

Preprint

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Twitter: @mjsikoraAuthors' contributions MJS, DMR, and SO conceived of the project and experiments. MJS, DMR, EKB, and HMH designed and performed experiments. MJS and DMR developed models for the project. All authors contributed to data analysis and interpretation. MJS wrote the draft manuscript; all authors read and revised the manuscript and have read and approved of this version of the manuscript. AbstractInvasive lobular carcinoma of the breast (ILC) is strongly estrogen-driven, and represents a unique context for estrogen receptor (ER) signaling. In ILC, ER controls the expression of the Wnt ligand WNT4, which is critical for endocrine response and anti-estrogen resistance, yet signaling mediated by WNT4 is poorly understood. We utilized reverse phase protein array (RPPA) to characterize ER and WNT4-driven signaling in ILC cells, and identified WNT4 as a mediator of downstream mTOR signaling via p70-S6K. Independent of mTOR/p70-S6K, ER and WNT4 control levels of MCL-1, which is associated with mitochondrial function. In this context, knockdown of WNT4 caused accumulation of reactive oxygen species and decreased ATP production that precede cell death. WNT4 regulation of both mTOR signaling and MCL-1 levels was also observed in anti-estrogen resistant models of ILC.Further, we identified that high WNT4 expression is associated with similar mTOR pathway activation in serous ovarian cancer tumors, suggesting that this WNT4 pathway is important in multiple tumor types.The identified downstream pathways represent potential targets to inhibit WNT4 signaling in ovarian cancer and overcome anti-estrogen resistance for patients with ILC.

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Section: Discussionmentioning

confidence: 79%

Estrogen controls mTOR signaling and mitochondrial function via WNT4 in lobular carcinoma cells

Shackleford

Bordeaux

et al. 2019

Preprint

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“…Lungs and pleura are addressed as common fields for breast cancer as first site of distal recurrence as well as one of the main targets during the meta-static process. 3 Despite the progress in oncological treatment, pleural metastasis of any primary malignancy is still associated with poor survival ranging from 3 to 12 months. [3][4][5] Malignant pleural effusion (MPE), resulting from direct infiltration of the pleura by cancer cells, develops in 2% to 11% of the patients with breast cancer within the metastatic course.…”

Section: Discussionmentioning

confidence: 99%

“…3 Despite the progress in oncological treatment, pleural metastasis of any primary malignancy is still associated with poor survival ranging from 3 to 12 months. [3][4][5] Malignant pleural effusion (MPE), resulting from direct infiltration of the pleura by cancer cells, develops in 2% to 11% of the patients with breast cancer within the metastatic course. 4 Moreover, pleural metastases occur within the first 5 years following the surgery for the underlying primary tumor at a rate of 80%.…”

Section: Discussionmentioning

confidence: 99%

A Well Disguised Pleural Metastasis of Breast Carcinoma

Sarıçam¹

2019

Turkiye Klinikleri J Case Rep

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elapse with distant metastasis occurs in 20% to 30% of patients with breast cancer within a period of 5 years after the surgery for the primary malignancy. 1 Moreover, approximately 20% of these cases develop isolated metastasis in the lung and the pleural space in the metastatic stage. 2 Herein, we present a patient with isolated pleural metastasis of breast carcinoma after a disease-free interval of 6 years. CASE REPORTA 58-year-old female admitted to our clinic with dyspnea ongoing progressively for the past two weeks. She shared history of left-sided breast invasive ductal carcinoma for which she underwent breast-sparing mastectomy and received adjuvant radiotherapy six years previously. Her routine follow-ups at the oncology clinic proved neither recurrence nor metastasis of her malignancy during this period. The medical history of this patient was unremarkable while the physical examination revealed decreased breathing sounds of the right hemithorax. A chest X-Ray showed massive pleural effusion which sequentially required drainage with an intrapleural catheter (Figure 1). The cytologic examination of the fluid introduced no evidence of malignancy. Moreover, microbial culture study did not report the growth of any pathological organisms, whereas mycobacterium culture of the effu-Turkiye Klinikleri J Case Rep. 2019;27(2):65-7 65 Re ce i ved:

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“…Late-presenting ILC has a distinct profile of distant metastatic sites. In ILC, transcoelemic spread leads to relative increase in frequency of gastrointestinal tract, peritoneal and ovarian metastases [13,43,44]. ILC that has spread to the gastrointestinal tract may present with gastrointestinal upset and bowel symptoms, including subacute and acute obstruction, while peritoneal disease may present with ascites, hydronephrosis and/or hydroureter.…”

Section: Diagnosis Of Lobular Breast Cancermentioning

confidence: 99%

“…ILC that has spread to the gastrointestinal tract may present with gastrointestinal upset and bowel symptoms, including subacute and acute obstruction, while peritoneal disease may present with ascites, hydronephrosis and/or hydroureter. In terms of the 'classic' sites of breast cancer metastases, there is relatively more metastasis to bone and skin and less to lungs and brain [43,44]. In patients on adjuvant therapy for ILC, or those being followed up post-adjuvant therapy, knowing the histological subtype is crucial in predicting the spread and monitoring for recurrence.…”

Section: Diagnosis Of Lobular Breast Cancermentioning

confidence: 99%

Invasive Lobular Breast Cancer as a Distinct Disease: Implications for Therapeutic Strategy

et al. 2019

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Invasive lobular carcinoma comprises 10-15% of all breast cancers and is increasingly recognised as a distinct and understudied disease compared with the predominant histological subtype, invasive ductal carcinoma. Hallmarks of invasive lobular carcinoma include E-cadherin loss, leading to discohesive morphology with cells proliferating in single-file strands and oestrogen receptor positivity, with favourable response to endocrine therapy. This review summarises the distinct histological and molecular features of invasive lobular carcinoma with focus on diagnostic challenges and the impact on surgical management and medical therapy. Emphasis is placed on recent advances in our understanding of the unique molecular biology of lobular breast cancer and how this is optimising our therapy approach in the clinic.

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Distinct Pattern of Metastases in Patients with Invasive Lobular Carcinoma of the Breast

Cited by 87 publications

References 24 publications

Estrogen controls mTOR signaling and mitochondrial function via WNT4 in lobular carcinoma cells

Estrogen controls mTOR signaling and mitochondrial function via WNT4 in lobular carcinoma cells

A Well Disguised Pleural Metastasis of Breast Carcinoma

Invasive Lobular Breast Cancer as a Distinct Disease: Implications for Therapeutic Strategy

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