I have heard the question asked on these boards, just how large must the invasive her2+ cancer be to warrent treatment with Herceptin?And do node negative T1 lesions really need Herceptin treatment? I find such questions very interesting because I had a very small 4mm invasive with only less than a micromets in the first node.
Perhaps the below link will convince some of you that it is the overexpression of her2 and mitotic index that may be more significant than the amount of invasive cancer involvement and the spread to the node that will ultimately determine prognosis. As the,"the six-year rate of relapse in early stage node negative bc in the below study was 40% for patients with highly positive tumors and 26% for those with weakly HER-2-expressing tumors ."Accordingly, the amount of hER-2 expression identifies a subgroup of node-negative breast cancer patients with the worst prognosis, who are candidates for specific intensive adjuvant therapy and might I add myself targeted therapy with herceptin as well.
Clearly, from all indications from the articles below, it appears we should be examining our pathology reports, looking at the CEP/Her2 ratio score for overexpression and at proliferation index for high tumor growth rates.
PS. I believe that a CEP/Her2 ratio over 4 is defined as highly overexpression of her2 and anything less than 4 is weakly overexpression of her2. Note the following from the full abstract,
Her2 expression and cell proliferation: prognostic markers in patients with node-negative breast cancer:
"We tested the pure prognostic value of
HER-2 overexpression, according to internationally proposed guidelines,
10,11 on the largest case series of node-negative breast cancer patients studied up to now. We failed to find a relevance of any cutoff value of
HER-2 overexpression on RFS-risk free survival. However, a breakdown analysis permitted us to attribute a discriminant prognostic power to
HER-2 overexpression within the subgroup of patients with rapidly proliferating tumors. In particular, patients with tumors in which a high proliferative activity was associated with
HER-2 overexpression showed a risk of relapse approximately two times higher than that observed for patients with rapidly proliferating but weak
HER-2-expressing tumors, or for those with slowly proliferating tumors regardless of
HER-2 expression.
In conclusion,
HER-2 expression and cell proliferation would seem to provide complementary prognostic information for node-negative breast cancer patients. Obviously, the clinical use of
HER-2 expression requires confirmation of our results in large prospectively planned studies, such as those already performed for cell proliferation.
9,20 "
Here's the abstract summary in full:
Her2 expression and cell proliferation: prognostic markers in patients with node-negative breast cancer.
Citation:
J Clin Oncol, United States; Vol 21, No 14 (Jul 15, 2003): pp. 2708-12
Affiliation:
Dept of Medical Oncology, Pierantoni Hospital, via Forlanini 34, 47100 Forlì, Italy. a.volpi@ausl.fo.it.
Authors:
Annalisa Volpi, Oriana Nanni, Franca De Paola, Anna Maria Granato, Annita Mangia, Franco Monti, Francesco Schittulli, Mario De Lena, Emanuela Scarpi, Paola Rosetti, Manlio Monti, Lorenzo Gianni, Dino Amadori, Angelo Paradiso
PURPOSE: We analyzed the clinical relevance of HER-2 expression, widely investigated in breast cancer but with contradictory results, in the largest case series of node-negative breast cancer patients investigated to date. PATIENTS AND METHODS: The pure prognostic value of HER-2 expression was investigated in 529 patients treated with locoregional therapy alone until early relapse. Proliferative activity was evaluated as [3H]thymidine labeling index and HER-2 expression by immunohistochemistry. All biologic determinations were conducted within the context of an intra- and interlaboratory National Quality Control Program. RESULTS: HER-2 expression was not related to relapse-free survival in the overall series but was a significant discriminant of prognosis in the subgroup of patients with rapidly proliferating tumors. Six-year rate of relapse was 40% for patients with highly (> or =30%) positive tumors and 26% for those with weakly HER-2-expressing tumors (P =.039). CONCLUSION: HER-2 expression in association with proliferative activity identifies a subgroup of node-negative breast cancer patients with the worst prognosis, who are candidates for specific intensive adjuvant therapy.
PS Let me just define proliferative activity of your tumor may be found by looking at the grade and mitotic index. As you know, the higer the mitotic index, the faster the tumor grows. See below article for information on that as well.
Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years.
Citation:
J Clin Oncol, United States; Vol 23, No 25 (9/2/2005): pp. 5993-6001
Affiliation:
Department of Pathology and Epidemiology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. baja@ier.no
Authors:
Baak, van Diest, Voorhorst, van der Wall, Beex, Vermorken, Janssen
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PURPOSE: To validate the independent strong prognostic value of mitotic activity index (MAI) in lymph node (LN) -negative invasive breast cancer patients younger than 55 years in a nationwide multicenter prospective study. PATIENTS AND METHODS: Analysis of routinely assessed MAI and other prognosticators in 516 patients (median follow-up, 118 months; range, 8 to 185 months), without systemic adjuvant therapy or previous malignancies. RESULTS: Distant metastases occurred in 127 patients (24.6%); 90 (17.4%) died as a result of metastases. MAI (< 10, > or = 10) showed strong association with recurrence (hazard ratio [HR], 3.12; 95% CI, 2.17 to 4.50; P < or = .0001) and mortality (HR, 4.42; 95% CI, 2.79 to 7.01; P < .0001). The absolute difference in 10-year Kaplan-Meier estimates of time to distant recurrence as well as survival was 22% between MAI less than 10 versus > or = 10. This effect was independent of age, estrogen receptor (ER) status, and tumor diameter (which were significant prognosticators). In multivariate analysis with regard to patient age, tumor diameter, grade, ER status, and the St Gallen criterion, MAI proved to be an independent and the strongest prognosticator. Tubular formation (TF) and nuclear atypia (NA), as constituents of (expert revised) grade, had no (for TF) or limited (for NA, P = .048) additional prognostic value to the MAI. In the group with MAI less than 10, MAI less than 3 versus more than 3 had additional value but the classical threshold of 0 to 5 v 6 to 10 did not. With this additional subdivision of MAI as less than 3, 3 to 9, and more than 9, NA lost its additive prognostic value. CONCLUSION: The MAI is the strongest, most widely available, easily assessable, inexpensive, well-reproducible prognosticator and is well suited to routinely differentiate between high- and low-risk LN-negative breast cancer patients younger than 55 years.
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