Precision medicine and personalized breast cancer: combination pertuzumab therapy

Trastuzumab (Herceptin), a monoclonal antibody directed against the human epidermal growth-factor receptor 2 (HER2), is the poster child for antibody-based targeted therapy in breast cancer. Pertuzumab, another humanized monoclonal antibody, binds to a different domain of HER2 and prevents the formation of HER2:HER3 dimers, which is the most potent heterodimer in the HER family. The combination of trastuzumab and pertuzumab has synergistic activity, and is associated with improved clinical outcomes. The US Food and Drug Administration (FDA) approved pertuzumab in combination with trastuzumab-based chemotherapy originally as first-line therapy for metastatic HER2-positive breast cancer in 2012, and more recently as neoadjuvant therapy for localized disease in 2013. Pertuzumab is the first neoadjuvant drug to receive accelerated approval by the FDA based on pathological complete response as the primary end point. In this article, we review the mechanism of action, pharmacokinetics, clinical efficacy, safety, and current role of pertuzumab in the management of breast cancer, as well as ongoing clinical trials and future directions regarding the utility of pertuzumab as a personalized therapeutic option for HER2-positive breast cancer. In the coming years, we anticipate increased utilization of neoadjuvant trials for drug development, biomarker discovery, and validation, and envision conduct of personalized breast cancer clinics in which therapies will be routinely selected based on genetic alterations in the tumor. Regardless of the targeted therapy combinations employed based on tumor genomic profile, trastuzumab and pertuzumab will likely continue to form the backbone of the personalized regimen for HER2-positive breast cancer

Patterns of Cellular Distribution with the Sentinel Node Positive for Breast Cancer

Background. Sentinel node biopsy (SNB) represents the standard of care in breast cancer axillary evaluation. Our study aims to characterize the patterns of malignant cell distribution within the sentinel nodes (SN). Methods. In a retrospective IRB-approved study, we examined the anatomic location of the nodal area with the highest radioactive signal or most intense blue staining (hot spot) and its distance from the metastatic foci. Results. 58 patients underwent SNB between January 2006 and February 2007. 12 patients with 19 positive SN were suitable for analysis. 4 (21%) metastases were located in the nodal hilum and 15 (79%) in the cortex. 6 (31%) metastases were found adjacent to the hotspot, and 9 (47%) within 4 mm of the hotspot. Conclusions. In our pilot series, SN metastases were within 4 mm of the hotspot in 78% of the cases. Pathologic analysis focused in that area may contribute to the more accurate identification of nodal metastases

Randomised controlled trial comparing hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors: a pilot study

Objectives: To compare the efficacy of hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors, and to evaluate the feasibility of conducting a clinical trial comparing a drug with a complementary or alternative method (CAM). Design: Prospective randomised trial. Setting: Breast health centre of a tertiary care centre. Participants: 15 women with a personal history of breast cancer or an increased risk of breast cancer who reported at least one daily hot flash. Interventions Gabapentin 900 mg daily in three divided doses (control) compared with standardised hypnotherapy. Participation lasted 8 weeks. Outcome measures The primary endpoints were the number of daily hot flashes and hot flash severity score (HFSS). The secondary endpoint was the Hot Flash Related Daily Interference Scale (HFRDIS). Results: 27 women were randomised and 15 (56%) were considered evaluable for the primary endpoint (n=8 gabapentin, n=7 hypnotherapy). The median number of daily hot flashes at enrolment was 4.5 in the gabapentin arm and 5 in the hypnotherapy arm. HFSS scores were 7.5 in the gabapentin arm and 10 in the hypnotherapy arm. After 8 weeks, the median number of daily hot flashes was reduced by 33.3% in the gabapentin arm and by 80% in the hypnotherapy arm. The median HFSS was reduced by 33.3% in the gabapentin arm and by 85% in the hypnotherapy arm. HFRDIS scores improved by 51.6% in the gabapentin group and by 55.2% in the hypnotherapy group. There were no statistically significant differences between groups. Conclusions: Hypnotherapy and gabapentin demonstrate efficacy in improving hot flashes. A definitive trial evaluating traditional interventions against CAM methods is feasible, but not without challenges. Further studies aimed at defining evidence-based recommendations for CAM are necessary. Trial registration clinicaltrials.gov (NCT00711529)

Advance Care Planning as a Shared Endeavor: Completion of ACP Documents in a Multidisciplinary Cancer Program

Objective—We examined the roles of oncology providers in advance care planning (ACP) delivery in the context of a multidisciplinary cancer program. Methods—Semi-structured interviews were conducted with 200 women with recurrent and/or metastatic breast or gynecologic cancer. Participants were asked to name providers they deemed important in their cancer care and whether they had discussed and/or completed ACP documentation. Evidence of ACP documentation was obtained from chart reviews. Results—Fifty percent of participants self-reported completing an advance directive (AD) and 48.5% had named a healthcare power of attorney (HPA), 38.5% had completed both, and 39.0% had completed neither document. Among women who self-reported completion of the documents, only 24.0% and 14.4% of women respectively had documentation of an AD and HPA in their chart. Completion of an AD was associated with number (adjusted odds ratio [AOR] = 1.49) and percentage (AOR = 6.58) of providers with whom the participant had a conversation about end-of-life decisions. Participants who named a social worker or nurse practitioner were more likely to report having completed an AD. Participants who named at least one provider in common (e.g., named the same oncologist) were more likely to have comparable behaviors related to naming a HPA (AOR = 1.13, p = 0.011) and completion of an AD (AOR = 1.06, p = 0.114). Conclusions—Despite the important role of physicians in facilitating ACP discussions, involvement of other staff was associated with a greater likelihood of completion of ACP documentation. Patients may benefit from opportunities to discuss ACP with multiple members of their cancer care team

Women and Sexuality: in Health and Sickness

Presentation given at the Haunting Histories of the Female Body Symposium held on November 17, 2006 in the Ferst Room, Georgia Tech Library. This session was part of Panel II: Gynecology and Women's Health: When Theory Meets PracticeRuntime: 36:48 minute