Breast cancer

Preclinical and clinical evaluation of intraductally administered agents in early breast cancer

Vered Stearns, Tsuyoshi Mori, Lisa Jacobs, Nagi Fouad Khouri, Edward Gabrielson, Takahiro Yoshida, Scott Kominsky, David L. Huso, Stacie Jeter, Penny Powers, Karineh Tarpinian, Regina J. Brown, Julie R Lange, Michelle Rudek-Renaut, Zhe Zhang, Theodore N. Tsangaris, Saraswati Sukumar

Research output: Contribution to journalArticle

Abstract

Most breast cancers originate in the epithelial cells lining the breast ducts. Intraductal administration of cancer therapeutics would lead to high drug exposure to ductal cells and eliminate preinvasive neoplasms while limiting systemic exposure. We performed preclinical studies in N-methyl-N′- nitrosourea-treated rats to compare the effects of 5-fluorouracil, carboplatin, nanoparticle albumin-bound paclitaxel, and methotrexate to the previously reported efficacy of pegylated liposomal doxorubicin (PLD) on treatment of early and established mammary tumors. Protection from tumor growth was observed with all five agents, with extensive epithelial destruction present only in PLD-treated rats. Concurrently, we initiated a clinical trial to establish the feasibility, safety, and maximum tolerated dose of intraductal PLD. In each eligible woman awaiting mastectomy, we visualized one ductal system and administered dextrose or PLD using a dose-escalation schema (2 to 10 mg). Intraductal administration was successful in 15 of 17 women with no serious adverse events. Our preclinical studies suggest that several agents are candidates for intraductal therapy. Our clinical trial supports the feasibility of intraductal administration of agents in the outpatient setting. If successful, administration of agents directly into the ductal system may allow for "breast-sparing mastectomy" in select women.

Original languageEnglish (US)
Article number106ra108
JournalScience Translational Medicine
Volume3
Issue number106
DOIs
StatePublished - Oct 26 2011

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Breast Neoplasms
Mastectomy
Breast
Clinical Trials
Methylnitrosourea
Neoplasms
Maximum Tolerated Dose
Carboplatin
Methotrexate
Fluorouracil
Nanoparticles
Outpatients
Therapeutics
Epithelial Cells
Safety
Glucose
liposomal doxorubicin
Growth
Pharmaceutical Preparations
Albumin-Bound Paclitaxel

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Breast cancer : Preclinical and clinical evaluation of intraductally administered agents in early breast cancer. / Stearns, Vered; Mori, Tsuyoshi; Jacobs, Lisa; Khouri, Nagi Fouad; Gabrielson, Edward; Yoshida, Takahiro; Kominsky, Scott; Huso, David L.; Jeter, Stacie; Powers, Penny; Tarpinian, Karineh; Brown, Regina J.; Lange, Julie R; Rudek-Renaut, Michelle; Zhang, Zhe; Tsangaris, Theodore N.; Sukumar, Saraswati.

In: Science Translational Medicine, Vol. 3, No. 106, 106ra108, 26.10.2011.

Research output: Contribution to journalArticle

Stearns, Vered ; Mori, Tsuyoshi ; Jacobs, Lisa ; Khouri, Nagi Fouad ; Gabrielson, Edward ; Yoshida, Takahiro ; Kominsky, Scott ; Huso, David L. ; Jeter, Stacie ; Powers, Penny ; Tarpinian, Karineh ; Brown, Regina J. ; Lange, Julie R ; Rudek-Renaut, Michelle ; Zhang, Zhe ; Tsangaris, Theodore N. ; Sukumar, Saraswati. / Breast cancer : Preclinical and clinical evaluation of intraductally administered agents in early breast cancer. In: Science Translational Medicine. 2011 ; Vol. 3, No. 106.
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