Background: The topic of trastuzumab therapy without chemotherapy in early breast cancer (EBC) has been repeatedly discussed at international consensus meetings, but is compromised by the lack of solid evidence from clinical studies.

We determined the concentration and effusion/serum ratio of mucin-like carcinoma-associated antigen (MCA) in comparison to carcinoembryonic antigen, carbohydrate antigen 19-9, cancer antigen 125, and cancer antigen 15-3 in 80 sera and 99 effusions from 64 patients with histologically confirmed malignancies (4 patients out of this group showed various effusions simultaneously, which were analyzed separately) and 31 patients with various nonneoplastic diseases. Tumor cells were detected by cytological examination in 41 effusions (60.3%) from patients with neoplastic diseases, while in another 27 cases this method failed to demonstrate the malignant origin of the effusion. Of the cytological "positive" malignant effusions 90% were also correctly identified by an elevated MCA concentration at a cutoff level of 10 U/ml, whereas only one effusion of benign origin (3%) showed a slightly elevated MCA concentration of 10.5 U/ml. In 33% of cytologically "negative" effusions of patients with neoplastic diseases, the MCA concentration was also elevated, with a maximum of 453 U/ml. Increased MCA levels in cytologically confirmed malignant effusions were not restricted to metastatic breast cancer. All 17 cytologically "positive" "non-breast cancer" effusions were correctly identified by their MCA concentrations. None of the other tumor markers reached this high sensitivity at the same level of specificity. The ratio of effusion/serum concentration of all tumor markers as well as the concentration of cancer antigen 125 in effusions was of little diagnostic value. Our results indicate that the MCA concentration in an effusion correlates very closely with its malignant origin and is superior to all the other antigens tested.(ABSTRACT TRUNCATED AT 250 WORDS)

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Die klinische Bedeutung ernes Tumormarkers hängt im wesentlichen von seiner Sensitivität und Spezifítät für eine bestimmte Tumorerkran-kung ab. Um den Stellenwert des kürzlich beschriebenen ‘mucin-like carcinoma-associated antigen’ bei der Betreuung von Mammakarzinom-Patientinnen zu untersuchen, bestimmten wir dessen Serumkon-zentration bei 50 Blutspendern, 130 Patienten mit verschiedenen benignen Erkrankungen, 138 Patienten mit unterschiedlichen metastasierten Tumoren sowie 137 Mammakarzinom-Patientinnen, wo von 78 eine bekannte Metastasierung aufwiesen, während die übrigen 59 nach chirurgischer und adjuvanter Primärtherapie rezidivfrei waren. Nur 2 % der Blutspender und 3 % der Patienten mit benignen Erkrankungen wiesen Serumspiegel oberhalb des Grenzwertes von 15 U/ml auf. Im Gegensatz dazu hatten 28 % der Patienten mit metastasierten Tumoren (außer Mammakarzinom) und 77% der Patientinnen mit metastasiertem Brustkrebs erhöhte MCA-Werte. Mammakarzinom-Patientinnen ohne Hinweis für Rezidiv wiesen in nur 3% der Fälle pathologische Markerspiegel auf. Bei Brustkrebs-Patientinnen waren die MCA-Konzentrationen vom Metastasierungstyp abhängig. Die höchsten Werte fanden sich bei einer gemischten Metastasierung, während ein isolierter Haut- oder Lymphknoten-Befall mit niedrigeren Serumspiegeln und der geringsten Sensitivität einherging. Da bei seriellen Bestimmungen eine gute Korrelation der Markerwerte mit dem Krankheitsverlauf besteht, halten wir MCA für einen geeigneten Parameter zur Verlaufskontrolle des metastasierten Mammakarzinoms. Aufgrund seiner hohen Sensitivität und Spezifítät könnte es sogar Vorteile gegenüber anderen bei dieser Erkrankung eingesetzten Markern aufweisen.

Purpose. Trastuzumab is part of the standard treatment in patients with human epidermal growth factor receptor 2-positive early breast cancer in addition to (neo)adjuvant chemotherapy. This German prospective noninterventional study, which included major patient cohorts underrepresented in the pivotal randomized studies, examined the generalizability of the results of those studies. Patients and Methods. Between 2006 and 2012, 4,027 patients were enrolled and treated with trastuzumab; they were unselected regarding age or concomitant/sequential adjuvant chemotherapy. Long-term outcome data were obtained in yearly intervals. All analyses were descriptive in nature. Results. Among 3,940 evaluable patients, 26% were elderly (older than 65 years of age). More than half of the population had pN0 tumor stage. Ninety-four percent received chemotherapy: 78% as adjuvant treatment and 14% as neoadjuvant treatment, 2% both. Anthracyclines were administered in 87% and taxanes in 66%. Trastuzumab was stopped prematurely in 9% (because of cardiotoxicity in 3.5%). Recurrence-free survival was 90.0% (95% confidence interval [CI], 88.9%-91.1%) and 82.8% (95% CI, 81.2%-84.4%) after 3 and 5 years, respectively. The corresponding figures for overall survival were 96.8% (95% CI, 96.1%-97.6%) and 90.0% (95% CI, 88.6%-91.4%). Pathological primary tumor size, lymph node involvement, and hormone receptor status had the greatest independent effect on recurrence risk. Cardiac function toxicity of National Cancer Institute common toxicity criteria grade 2 and 3 was observed in 2.5% and less than 1% of patients, respectively. Conclusion. The maturing follow-up data seem to confirm the beneficial results of trastuzumab treatment for early breast cancer from the randomized studies. Moreover, these findings support use of trastuzumab-based therapy in patients groups less commonly included in the phase III trials (e.g., elderly patients and those with stage I disease). The Oncologist 2017;22:131-138 Implications for Practice: On the basis of the results of large pivotal phase III studies, the inclusion of trastuzumab in adjuvant treatment regimens for human epidermal growth factor receptor 2-positive breast cancer is standard of care. However, in these trials, elderly patients, those with comorbidities, and/or those with contraindications or refusal of cytotoxic chemotherapy are typically underrepresented. This study provides data on observed treatment options, outcomes, and risks in a wider, unselected patient population (including more than 1,000 patients with stage I disease), treated routinely in several institutions of varying size and location across Germany.