for those finished with chemo wondering how important it is to have antihormonal

[Lani]

therapy in addition to herceptin, a new retrospective study concluded the following:


We showed that adding hormonal therapy to the combination of preoperative and/or postoperative chemotherapy and trastuzumab confers a survival benefit to patients with HR-positive/HER2-positive primary breast cancer. A noteworthy fact is that both AI and tamoxifen had an equivalent effect on prognosis for this patient population.
Since the U.S. Food and Drug Administration approved the use of trastuzumab in the adjuvant setting in November 2006, patients with HR-positive/HER2-positive primary breast cancer have received three-pronged treatments of the type examined here in clinical practice. However, no previous study has shown that adding adjuvant hormonal therapy to the combination of chemotherapy and anti-HER2 agents yields quantifiable advantages, and it is not possible to perform a randomized prospective study of this question because it is unethical to randomize someone out of the current standard of care. Therefore, we had to retrospectively assess the possible benefits of adding hormonal therapy in this patient population. In both univariate and multivariate analysis, we found that the three-pronged treatment provided significant improvement in DFS rates and a similar trend in OS rates, compared with chemotherapy and trastuzumab therapy without hormonal therapy.
Our results also indicate that any cross-talk that occurs between ER and HER2 is insufficient to degrade the effects of adding hormonal therapy to the chemotherapy-trastuzumab combination. Furthermore, we found that the specific hormonal agent used did not affect this finding. This result is in contrast to some previous results. For instance, others have asserted that the cross-talk between ER and HER2 is bidirectional and may cause resistance to both AI and tamoxifen in patients with HR-positive/HER2-positive breast cancer [15–17]. Dowsett et al. [24] found no significant benefit from adding tamoxifen to chemotherapy and trastuzumab for patients with HR-positive/HER2-positive breast cancer. However, as they noted, the number of patients (n = 75) was small and tamoxifen was administered for only 2 years. Furthermore, that study used a unique definition of HR positivity (H-score), making it difficult to compare those findings with others. Therefore, our results will provide a different perspective to this area of study.

The first randomized phase III study, the TAnDEM trial [26], revealed that the combination of trastuzumab and anastrozole resulted in a significantly longer median progression-free survival time (4.8 vs. 2.4 months, p = 0.0016) and a higher overall response rate (20.3 vs. 6.8 %) than did anastrozole alone in patients with HR-positive/HER2-positive metastatic breast cancer [26].
Our results showed that the triple combination of hormonal therapy, an anti-HER2 agent, and chemotherapy is the most effective treatment in HR-positive/HER2-positive primary breast cancer in the adjuvant setting. This treatment appears to effectively block tumor cell proliferation and growth and improve prognosis over that conferred by monotherapy or the combination of any two of the agents, even if cross-talk does exist between the ER- and HER2-signaling pathways. Recently, Montemurro et al. [27] demonstrated a progression-free survival benefit was gained by adding hormonal therapy to chemotherapy and trastuzumab in patients with metastatic breast cancer (p = 0.007). In that study, trastuzumab was given not in a neoadjuvant or adjuvant setting but in a metastatic setting. We could show similar benefit of adding hormonal therapy in an adjuvant setting. Furthermore, we demonstrated the benefit of receiving hormonal therapy whether in the form of an AI or tamoxifen. Taken together, our findings and theirs suggest that adding hormonal therapy confer benefits regardless of the extent of disease.
There were some limitations to this retrospective study. First, the prescription of AIs is limited to postmenopausal women, but our study included both premenopausal and postmenopausal women. However, because age and menopausal status had no significant effect in terms of DFS and OS rates, we believe this limitation did not affect our results. This is also supported by the fact that the AI and tamoxifen groups did not differ. Second, we could not assess the association between quantitative expression levels of ER or PR and prognosis. We used a cutoff value of 10 % to define ER or PR positivity because all patients’ disease was were diagnosed before the American Society for Clinical Oncology’s revisions to the definition, and treatment had been performed accordingly. Our population also included patients from hospitals that did not include a quantitative expression level in the patients’ medical records. However, we believe our results can be applied in clinical practice even without those quantitative assessments because of the very low revised cutoff values from the American Society of Clinical Oncology and the College of American Pathologists, which recommend that ER and PR assays be considered positive if even 1 % of tumor nuclei in a sample are positive [28]. Third, many patients did not receive hormonal therapy in this study. Although we could not find records describing whether low HR expression had influenced the prescription of hormone therapy or patients’ refusal, not receiving hormone therapy as well as the level of HR expression might have affected the prognosis in this population.
Because there are signaling pathways influenced by both ER and HER2, additional molecules could be targeted to overcome more cross-talk and further boost response. ER regulates cellular proliferation and survival through genomic and nongenomic signaling pathways [5, 29]. Phosphorylation of HER2 activates downstream signaling pathways, including the PI3K/Akt/mTOR and mitogen-activated protein pathways [30]. Cross-talk thus exists not only between ER and HER2 but also among other epidermal growth factor families [5]. To further block interaction between ER and HER2 signaling pathways, one could combine novel agents targeting these signaling pathways, e.g., mTOR inhibitors, with hormonal therapy; this approach has great potential to further benefit patients with HR-positive/HER2-positive breast cancer.
In summary, we report that hormonal therapy, whether with an AI or tamoxifen, added to the combination of preoperative or postoperative chemotherapy and trastuzumab improves the prognosis of patients with HR-positive/HER2-positive primary breast cancer. Preoperative and/or postoperative chemotherapy and trastuzumab without adjuvant hormonal therapy is an inferior treatment for this patient group.

To read the whole article:

put the PMID number at the end of the following abstract of the article into the search box of PUBMED after googling ENTREZ PUBMED

Breast Cancer Res Treat. 2012 Nov 27. [Epub ahead of print]
Adding hormonal therapy to chemotherapy and trastuzumab improves prognosis in patients with hormone receptor-positive and human epidermal growth factor receptor 2-positive primary breast cancer.
Hayashi N, Niikura N, Yamauchi H, Nakamura S, Ueno NT.
Source
Department of Breast Medical Oncology, Unit 1354, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Abstract
Adjuvant hormonal therapy for hormone receptor (HR)-positive primary breast cancer patients and a human epidermal growth factor receptor 2 (HER2)-targeted agent for HER2-positive primary breast cancer patients are standard treatment. However, it is not well known whether adding hormonal therapy to the combination of preoperative or postoperative chemotherapy and HER2-targeted agent contributes any additional clinical benefit in patients with HR-positive/HER2-positive primary breast cancer regardless of cross-talk between HR and HER2. We retrospectively reviewed records from 897 patients with HR-positive/HER2-positive primary breast cancer with clinical stage I-III disease who underwent surgery between 1988 and 2009. We determined the overall survival (OS) and disease-free survival (DFS) rates according to whether they received hormonal therapy or not and according to the type of hormonal therapy, tamoxifen and aromatase inhibitor, they received. The median followup time was 52.8 months (range 1-294.6 months). Patients who received hormonal therapy with chemotherapy and trastuzumab (n = 128) had significantly higher OS and DFS rates than did those who received only chemotherapy and trastuzumab (n = 46) in log-rank analysis (OS 96.1 vs. 87.0 %, p = 0.023, DFS 86.7 vs. 78.3 %, p = 0.029). There was no statistical difference in OS or DFS between those given an aromatase inhibitor and those given tamoxifen. In multivariate analysis, receiving hormonal therapy in addition to the combination of chemotherapy and trastuzumab was the sole independent prognostic factor for DFS (hazard ratio 0.446; 95 % CI 0.200-0.992; p = 0.048), and there was a similar trend in OS. Our study supported that hormonal therapy, whether in the form of an aromatase inhibitor or tamoxifen, confers a survival benefit when added to chemotherapy and trastuzumab in patients with HR-positive/HER2-positive primary breast cancer. Adjuvant treatment without hormonal therapy is inferior for this patient population.
PMID: 23184079

[karen z]

Lani,
Thanks so much for posting.

[1rarebird]

Based on this report it sounds like anyone who is about to start chemo and Herceptin and are ER+ should consider asking their oncoogist if they could be better off by starting the hormonal therapy immediately along with the chemo and H. In my case I don't believe the additional side effects from Tamoxifen while on chemo would have been bad enough to warrant holding off until finishing with chemo. I believe these findings are suggestive that ER and Her2 cross-talk is a real issue that needs to be addressed during treatment.--bird