3 augustus 2011: wat veel vrouwen en ook artsen niet weten of niet willen bekennen is dat door behandelingen en medicijnen de status van de tumoren van borstkanker kan veranderen. Leest u eens onderstaand artikel. De helft van de vrouwen uit deze studie hadden een verschillende status tussen diagnose van primaire tumor en een meting jaren later. De moeite waard dus om bij falen van een bepaalde behandeling of middel een nieuwe status te laten meten.

12 mei 2010: Bron: Ann Oncol. 2009 Nov 3.

De status van de oestrogeen receptor (ER), progesteron receptor (PR) en human epidermal growth factor receptor 2 (HER2) van borstkanker wordt standaard gebruikt voor het bepalen van een behandelingsstrategie. Nu blijkt dat bij vrouwen met uitgezaaide borstkanker de status van deze receptoren voor hun primaire tumor vaak anders ligt dan voor de uitzaaiingen. En ook blijkt dat de status van deze receptoren zich snel en vaker dan gedacht aanpassen en veranderen door de behandelingen. Dit blijkt uit een gerandomiseerde studie bij 385 vrouwen met invasieve borstkanker. 211 van die vrouwen hadden ook uitzaaiingen. Maar liefst 46,9 % van de vrouwen hadden een verschillende status tussen primaire tumor en uitzaaiingen.

Het onderzoeksteam analyseerde de expressie van 3 receptoren: oestrogeenreceptor (ER), progesteron receptor, en humane epidermale groei factor receptor 2 (HER2). De expressie van deze worden gebruikt om beslissingen te nemen over adjuvante therapie bij borstkanker; ER-positieve patiënten word meestal  hormonale therapie (tamoxifen en / of aromataseremmers) aangeboden en HER2-positieve patiënten worden trastuzumab (Herceptin) aangeboden.

Deze behandelings beslissingen worden genomen op basis van de receptor status in de primaire tumor, verkregen uit een diagnostische rechtstreekse biopsie of uit weefsel dat chirurgisch is verwijderd. Maar als de borstkanker al is uitgezaaid of zich nog verder verspreidt, kunnen de kenmerken van de receptoren ervan wijzigen. Verschillende studies hebben dit verschil in status onderzocht en aangetoond. 


In deze laatste studie wordt een verandering in bijna de helft van de onderzochte patiënten (46,9%) aangetoond. En blijken nogal wat vrouwen emt borstkanker dus verkeerd te worden behandeld. Of heeft de eerste behandeling een dusdanig effect dat de receptorstatus verandert.

Lees hier een artikel in Medscape over deze studie.

Ann Oncol. 2009 Nov 3. [Epub ahead of print]

Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases.

Aitken SJ, Thomas JS, Langdon SP, Harrison DJ, Faratian D.

Edinburgh Breakthrough Research Unit and Division of Pathology, University of Edinburgh, Edinburgh, UK.

Abstract

BACKGROUND: Assessment of receptors [estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)] is routinely carried out on primary tumour in order to select appropriate adjuvant therapy; the same analysis is not carried out on nodal metastases. Since de novo resistance to therapy is common, we quantified differences in receptor expression between primary and nodal disease in order to assess whether this might contribute to therapeutic resistance.

PATIENTS AND METHODS: A total of 385 patients with invasive primary breast carcinomas and paired lymph nodes (n = 211) were assessed for ER, PR and HER2 expression using quantitative immunofluorescence. Cut-points were defined by comparison with tumours scored by immunohistochemistry (IHC) and FISH. Differences in expression for each of the markers and molecular phenotype were analysed.

RESULTS: Quantitative receptor expression shows a wide dynamic range compared with IHC. Overall, 46.9% cases had disparate breast/node receptor status of at least one receptor. Many of the differences in expression between primary tumour and node are large magnitude (greater than fivefold) changes. Triple-negative phenotype changes in 23.1% of cases.

CONCLUSIONS: A significant number of patients show discordant quantitative expression of molecular markers between primary and nodal disease. Appropriately measured, lymph node receptor status could be a more accurate measurement for guiding adjuvant therapy, which requires testing in a clinical trial.

PMID: 19858088 [PubMed - as supplied by publisher]

 

Ann Oncol. 2009 Nov 3. [Epub ahead of print]

Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases.

Aitken SJ, Thomas JS, Langdon SP, Harrison DJ, Faratian D.

Edinburgh Breakthrough Research Unit and Division of Pathology, University of Edinburgh, Edinburgh, UK.

Abstract

BACKGROUND: Assessment of receptors [estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)] is routinely carried out on primary tumour in order to select appropriate adjuvant therapy; the same analysis is not carried out on nodal metastases. Since de novo resistance to therapy is common, we quantified differences in receptor expression between primary and nodal disease in order to assess whether this might contribute to therapeutic resistance.

PATIENTS AND METHODS: A total of 385 patients with invasive primary breast carcinomas and paired lymph nodes (n = 211) were assessed for ER, PR and HER2 expression using quantitative immunofluorescence. Cut-points were defined by comparison with tumours scored by immunohistochemistry (IHC) and FISH. Differences in expression for each of the markers and molecular phenotype were analysed.

RESULTS: Quantitative receptor expression shows a wide dynamic range compared with IHC. Overall, 46.9% cases had disparate breast/node receptor status of at least one receptor. Many of the differences in expression between primary tumour and node are large magnitude (greater than fivefold) changes. Triple-negative phenotype changes in 23.1% of cases.

CONCLUSIONS: A significant number of patients show discordant quantitative expression of molecular markers between primary and nodal disease. Appropriately measured, lymph node receptor status could be a more accurate measurement for guiding adjuvant therapy, which requires testing in a clinical trial.

PMID: 19858088 [PubMed - as supplied by publisher]

We confirmed that loss of HER2-positive status in metastatic tumors can occur in patients with primary HER2-positive breast cancer. Our data strongly support the need for biopsies of metastatic lesions to accurately determine patient prognosis and appropriate use of targeted therapy

Source: Journal of Clinical Oncology

Loss of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Metastatic Sites of HER2-Overexpressing Primary Breast Tumors

  1. Naoki Niikura,
  2. Jun Liu,
  3. Naoki Hayashi,
  4. Elizabeth A. Mittendorf,
  5. Yun Gong,
  6. Shana L. Palla,
  7. Yutaka Tokuda,
  8. Ana M. Gonzalez-Angulo,
  9. Gabriel N. Hortobagyi and
  10. Naoto T. Ueno

+ Author Affiliations

  1. Naoki Niikura, Jun Liu, Naoki Hayashi, Elizabeth A. Mittendorf, Yun Gong, Shana L. Palla, Ana M. Gonzalez-Angulo, Gabriel N. Hortobagyi, and Naoto T. Ueno, The University of Texas MD Anderson Cancer Center, Houston, TX; and Naoki Niikura and Yutaka Tokuda, Tokai University School of Medicine, Kanagawa, Japan.
  1. Corresponding author: Naoto T. Ueno, MD, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1354, Houston, TX 77030; e-mail: nueno@mdanderson.org.

Abstract

Purpose We evaluated whether patients with human epidermal growth factor receptor 2 (HER2) –positive primary breast tumors had metastatic tumors that were HER2 positive (concordant) or HER2 negative (discordant). We then evaluated whether treatment with trastuzumab or chemotherapy before biopsy of the metastasis had any effect on the rate of HER2 discordance. We also compared the overall survival durations of patients with HER2-concordant and -discordant tumors.

Patients and Methods We retrospectively identified all patients who initially had been diagnosed with HER2-positive (immunohistochemistry 3+ and/or fluorescent in situ hybridization positive) primary breast cancer between 1997 and 2008 at MD Anderson Cancer Center who also had metastatic tumor biopsy results available for review.

Results We included 182 patients who met our criteria. Forty-three (24%) of the 182 patients with HER2-positive primary tumors had HER2-negative metastatic tumors. The HER2 discordance rates differed significantly on the basis of whether patients received chemotherapy (P = .022) but not on the basis of whether patients received trastuzumab (P = .296). Patients with discordant HER2 status had shorter overall survival than did patients with concordant HER2 status (hazard ratio , 0.43; P = .003). A survival difference remained among the 67 patients who received trastuzumab (HR, 0.56; P = .083) and 101 patients who did not (HR, 0.53; P = .033) before their metastasis biopsies.

Conclusion We confirmed that loss of HER2-positive status in metastatic tumors can occur in patients with primary HER2-positive breast cancer. Our data strongly support the need for biopsies of metastatic lesions to accurately determine patient prognosis and appropriate use of targeted therapy.


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