Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

Breast metastases from rectal carcinoma

Metastases to the breast from extramammary neoplasms are very rare, constituting 2.7% of all malignant breast tumours. The most common primary tumor metastatic to the breast is primary breast cancer. Rectal cancer metastasizing to the breast is extremely rare. We report a case of aggressive rectal carcinoma with metastasis to the breast.

Colorectal cancer metastatic to the breast:A case report

BACKGROUND Breast metastases from colorectal cancer(CRC)are very uncommon.There is no unanimous consensus regarding the best treatment for this rare condition,and management is,especially in elderly patients,limited to diagnosis and palliative care.Capecitabine,an oral fluoropyrimidine derivative,might be helpful in controlling the disease and may be a treatment option for patients unable to receive more aggressive chemotherapy.CASE SUMMARY We report a case of synchronous massive breast metastasis from CRC in an 85 year old patient who came to the hospital presenting a huge mass originating from the axillary extension of the right breast.A whole body computed tomography also showed a mass in the right colon.The patient underwent a simple right mastectomy along with right hemicolectomy.The resected breast showed massive metastasis from CRC with intense and homogeneous nuclear CDX2 staining,while the colon specimen revealed poorly differentiated adenocarcinoma stage pT4a pN0 pM1(breast)(Tumor Node Metastasis 2017).Three months later she developed a subcutaneous mass at the site of the previous mastectomy.An ultrasound guided biopsy was carried out again and revealed a metastasis from CRC.The patient then started treatment with capecitabine plus bevacizumab,obtaining stable disease(RECIST criteria)and a clinical benefit after 3 mo of therapy.CONCLUSION In our experience,capecitabine and bevacizumab may be a useful treatment option for breast metastases from primary CRC in elderly patients.

Successful outcome after combined chemotherapeutic and surgical management in a case of esophageal cancer with breast and brain relapse

Esophageal cancer (EC) is a highly lethal disease. Approximately 50% of patients present with metastatic EC and most patients with localized EC will have local recurrence or develop metastases, despite potentially curative local therapy. The most common sites of distant recurrence are represented by lung, liver and bone while brain and breast metastases are rare. Usually patients with advanced disease are not treated aggressively and their median survival is six months. We report a woman patient who developed breast and brain metastases after curative surgery. We treated her with a highly aggressive chemotherapeutic and surgical combination resulting in a complete remission of the disease even after 11-year follow-up. We think that in super selected patients with more than one metastasis, when functional status is good and metastases are technically resectable, a surgical excision may be considered as a salvage option and chemotherapy should be delivered to allow a systemic control.

Staging the axilla in women with breast cancer: the utility of preoperative ultrasound-guided needle biopsy

Preoperative staging of the axilla in women with invasive breast cancer using ultrasound-guided needle biopsy(UNB) identifies approximately 50% of patients with axillary nodal metastases prior to surgical intervention. Although moderately sensitive, it is a highly specific staging strategy that is rarely falsely-positive, hence a positive UNB allows patients to be triaged to axillary lymph-node dissection(ALND) avoiding potentially unnecessary sentinel node biopsy(SNB). In this review, we extend our previous work through an updated literature search, focusing on studies that report data on UNB utility. Based on data for 10,934 breast cancer patients, sourced from 35 studies, a positive UNB allowed triage of 1,745 cases(simple proportion 16%) to axillary surgical treatment: the utility of UNB was a median 19.8% [interquartile range(IQR) 11.6%-26.7%] across these studies. We also modelled data from a subgroup of studies, and estimated that amongst patients with metastases to axillary nodes, the odds ratio(OR) for high nodal disease burden for a positive UNB versus a negative UNB was 4.38 [95% confidence interval(95% CI): 3.13, 6.13], P<0.001. From this model, the estimated proportion with high nodal disease burden was 58.9%(95% CI: 50.2%, 67.0%) for a positive UNB, whereas the estimated proportion with high nodal disease burden was 24.6%(95% CI: 17.7%, 33.2%) if UNB was negative. Overall, axillary UNB has good clinical utility and a positive UNB can effectively triage to ALND. However, the evolving landscape of axillary surgical treatment means that UNB will have relatively less utility where surgeons have modified their practice to omission of ALND for minimal nodal metastatic disease.

Nanomaterials with dual immunomodulatory functions for synergistic therapy of breast cancer brain metastases

A long-standing paucity of effective therapies results in the poor outcomes of triple-negative breast cancer brain metastases.Immunotherapy has made progress in the treatment of tumors,but limited by the non-immunogenicity of tumors and strong immunosuppressive environment,patients with TNBC brain metastases have not yet benefited from immunotherapy.Dual immunoregulatory strategies with enhanced immune activation and reversal of the immunosuppressive microenvironment provide new therapeutic options for patients.Here,we propose a cocktail-like therapeutic strategy of microenvironment regulation-chemotherapy-immune synergistic sensitization and construct reduction-sensitive immune microenvironment regulation nanomaterials(SIL@T).SIL@T modified with targeting peptide penetrates the BBB and is subsequently internalized into metastatic breast cancer cells,releasing silybin and oxaliplatin responsively in the cells.SIL@T preferentially accumulates at the metastatic site and can significantly prolong the survival period of model animals.Mechanistic studies have shown that SIL@T can effectively induce immunogenic cell death of metastatic cells,activate immune responses and increase infiltration of CD8+T cells.Meanwhile,the activation of STAT3 in the metastatic foci is attenuated and the immunosuppressive microenvironment is reversed.This study demonstrates that SIL@T with dual immunomodulatory functions provides a promising immune synergistic therapy strategy for breast cancer brain metastases.

Management of breast cancer brain metastases: Focus on human epidermal growth factor receptor 2-positive breast cancer

After the introduction of trastuzumab, a monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER2), the overall survival (OS) among patients with HER2-positive breast cancer has been substantially improved. However, among these patients, the incidence of brain metastases (BM) has been increasing and an increased proportion of them have died of intracranial progression, which makes HER2-positive breast cancer brain metastases (BCBM) a critical issue of concern. For local control of limited BM, stereotactic radiosurgery (SRS) and surgical resection are available modalities with different clinical indications. Postoperative or preoperative radiation is usually delivered in conjunction with surgical resection to boost local control. Adjuvant whole-brain radiotherapy (WBRT) should be deferred for limited BM because of its impairment of neurocognitive function while having no benefit for OS. Although WBRT is still the standard treatment for local control of diffuse BM, SRS is a promising treatment for diffuse BM as the technique continues to improve. Although large molecules have difficulty crossing the blood brain barrier, trastuzumab-containing regimens are critical for treating HER2-positive BCBM patients because they significantly prolong OS. Tyrosine kinase inhibitors are more capable of crossing into the brain and they have been shown to be beneficial for treating BM in HER2-positive patients, especially lapatinib combined with capecitabine. The antiangiogenic agent, bevacizumab, can be applied in the HER2-positive BCBM scenario as well. In this review, we also discuss several strategies for delivering drugs into the central nervous system and several microRNAs that have the potential to become biomarkers of BCBM.

Escape from abluminal LRP1-mediated clearance for boosted nanoparticle brain delivery and brain metastasis treatment

Breast cancer brain metastases(BCBMs)are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth.Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable bloodbrain barrier(BBB).Accumulation studies prove that low density lipoprotein receptor-related protein 1(LRP1)is promising target for BBB transcytosis.However,as the primary clearance receptor for amyloid beta and tissue plasminogen activator,LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics.Matrix metalloproteinase-1(MMP1)is highly enriched in metastatic niche to promote growth of BCBMs.Herein,it is reported that nanoparticles(NPs-K-s-A)tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2(A),can surmount the BBB and escape LRP1-mediated clearance in metastatic niche.NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice,while comparable brain accumulation in normal mice.The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs.Due to the efficient BBB penetration,special and remarkable clearance escape,and facilitated therapeutic outcome,the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.