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Combined Antiangiogenic and Mammalian Target of Rapamycin Inhibitor Targeted Therapy in Metaplastic Breast Cancer Harboring a PIK3CA Mutation.

Agarwal R, Koenig K, Rohren E, Subbiah V - J Breast Cancer (2014)

Bottom Line: Partial remission was achieved.In this report, the scientific rationale underlying the activity of this combination was explored.In conclusion, patients may benefit from being offered molecular profiling early during the course of the disease to receive a therapy guided accordingly.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, University of Cincinnati College of Medicine, Cincinnati, USA.

ABSTRACT
Metaplastic breast cancer (MpBC) is an extremely rare breast cancer subtype, characterized by a heterogeneous phenotype. MpBC aggressive biology is attributed to its stem cell-like characteristics. Since these tumors are largely chemoresistant, novel targeted therapies should be explored. Herein, we report the clinical course of a 59-year-old African American woman with MpBC with a PIK3CA mutation in codon 545, exon 10 (GAG to AAG; p.Glu545Lys) and a TP53 mutation in codon 286, exon 8 (GAA to AAA; p.Glu286Lys). The same mutations were observed in the primary and secondary sites. The patient was treated with a molecularly matched therapy using a combined antiangiogenic and mammalian target of rapamycin kinase inhibitor strategy that included liposomal doxorubicin, bevacizumab, and temsirolimus. Partial remission was achieved. In this report, the scientific rationale underlying the activity of this combination was explored. In conclusion, patients may benefit from being offered molecular profiling early during the course of the disease to receive a therapy guided accordingly.

No MeSH data available.


Related in: MedlinePlus

Pretreatment and posttreatment maximum intensity projection image and coronal images of the patient. Pretreatment maximum intensity projection image and coronal image showing hypermetabolic pulmonary metastasis and lymphadenopathy (A, B). Posttreatment maximum intensity projection image and coronal image showing response to therapy after two cycles of combination of liposomal doxorubicin, bevacizumab, and temsirolimus (C, D).
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Figure 3: Pretreatment and posttreatment maximum intensity projection image and coronal images of the patient. Pretreatment maximum intensity projection image and coronal image showing hypermetabolic pulmonary metastasis and lymphadenopathy (A, B). Posttreatment maximum intensity projection image and coronal image showing response to therapy after two cycles of combination of liposomal doxorubicin, bevacizumab, and temsirolimus (C, D).

Mentions: The patient was given a combination therapy of intravenous temsirolimus, 25 mg weekly, plus intravenous bevacizumab, 15 mg/kg, and liposomal doxorubicin, 20 mg/m2, once on day 1 every 21 days [5]. The patient tolerated the regimen reasonably well with the exception of grade 1 fatigue. Repeat positron emission tomography/computed tomography (PET/CT) after two cycles of therapy showed a decrease in the standard uptake value from 12.3 to 3.9 in one intrathoracic lymph node and a decrease from 13.1 to 7.0 in another lesion as well as the complete resolution of the disease in most of the sites on a PET scan, with corresponding anatomic improvement observed on a CT scan (Figures 1,2,3). On the basis of the response, the therapy was pursued. PET/CT or CT-Chest/Abdomen/Pelvis was performed every 2 months to evaluate the response. After seven cycles, the patient requested a month break from chemotherapy related to grade 2-3 fatigue. The patient resumed her therapy with reasonable tolerance and continued with clinical benefit and radiological response. After 14 cycles of therapy, a plateau of response was reached and the patient developed grade 4 dyspnea. The scans indicated the progression of the disease and the therapy was discontinued.


Combined Antiangiogenic and Mammalian Target of Rapamycin Inhibitor Targeted Therapy in Metaplastic Breast Cancer Harboring a PIK3CA Mutation.

Agarwal R, Koenig K, Rohren E, Subbiah V - J Breast Cancer (2014)

Pretreatment and posttreatment maximum intensity projection image and coronal images of the patient. Pretreatment maximum intensity projection image and coronal image showing hypermetabolic pulmonary metastasis and lymphadenopathy (A, B). Posttreatment maximum intensity projection image and coronal image showing response to therapy after two cycles of combination of liposomal doxorubicin, bevacizumab, and temsirolimus (C, D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4197360&req=5

Figure 3: Pretreatment and posttreatment maximum intensity projection image and coronal images of the patient. Pretreatment maximum intensity projection image and coronal image showing hypermetabolic pulmonary metastasis and lymphadenopathy (A, B). Posttreatment maximum intensity projection image and coronal image showing response to therapy after two cycles of combination of liposomal doxorubicin, bevacizumab, and temsirolimus (C, D).
Mentions: The patient was given a combination therapy of intravenous temsirolimus, 25 mg weekly, plus intravenous bevacizumab, 15 mg/kg, and liposomal doxorubicin, 20 mg/m2, once on day 1 every 21 days [5]. The patient tolerated the regimen reasonably well with the exception of grade 1 fatigue. Repeat positron emission tomography/computed tomography (PET/CT) after two cycles of therapy showed a decrease in the standard uptake value from 12.3 to 3.9 in one intrathoracic lymph node and a decrease from 13.1 to 7.0 in another lesion as well as the complete resolution of the disease in most of the sites on a PET scan, with corresponding anatomic improvement observed on a CT scan (Figures 1,2,3). On the basis of the response, the therapy was pursued. PET/CT or CT-Chest/Abdomen/Pelvis was performed every 2 months to evaluate the response. After seven cycles, the patient requested a month break from chemotherapy related to grade 2-3 fatigue. The patient resumed her therapy with reasonable tolerance and continued with clinical benefit and radiological response. After 14 cycles of therapy, a plateau of response was reached and the patient developed grade 4 dyspnea. The scans indicated the progression of the disease and the therapy was discontinued.

Bottom Line: Partial remission was achieved.In this report, the scientific rationale underlying the activity of this combination was explored.In conclusion, patients may benefit from being offered molecular profiling early during the course of the disease to receive a therapy guided accordingly.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, University of Cincinnati College of Medicine, Cincinnati, USA.

ABSTRACT
Metaplastic breast cancer (MpBC) is an extremely rare breast cancer subtype, characterized by a heterogeneous phenotype. MpBC aggressive biology is attributed to its stem cell-like characteristics. Since these tumors are largely chemoresistant, novel targeted therapies should be explored. Herein, we report the clinical course of a 59-year-old African American woman with MpBC with a PIK3CA mutation in codon 545, exon 10 (GAG to AAG; p.Glu545Lys) and a TP53 mutation in codon 286, exon 8 (GAA to AAA; p.Glu286Lys). The same mutations were observed in the primary and secondary sites. The patient was treated with a molecularly matched therapy using a combined antiangiogenic and mammalian target of rapamycin kinase inhibitor strategy that included liposomal doxorubicin, bevacizumab, and temsirolimus. Partial remission was achieved. In this report, the scientific rationale underlying the activity of this combination was explored. In conclusion, patients may benefit from being offered molecular profiling early during the course of the disease to receive a therapy guided accordingly.

No MeSH data available.


Related in: MedlinePlus