Trastuzumab‐associated cardiotoxicity

Keefe, M

doi:10.1002/cncr.10854

Cited by 320 publications

(200 citation statements)

References 33 publications

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“…To date, we do not know the true incidence of trastuzumab cardiac toxicity when it is given alone or with other antineoplastic drugs; the ongoing clinical trials, with careful cardiac monitoring, are likely to give us more accurate information Speyer, 2002. The mechanism of trastuzumab cardiotoxicity is unknown (Ewer et al, 1999;Keefe et al, 2002;Seidman et al, 2002) and the pathogenesis and histologic changes responsible for trastuzumab-associated cardiotoxicity are currently under investigation. Understanding the mechanisms of the trastuzumabassociated cardiotoxicity is important to provide strategies for the prevention or identification of patients at risk for cardiac complications.…”

Section: Discussionmentioning

confidence: 99%

Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer

Gori¹,

Colozza²,

Mosconi³

et al. 2004

Br J Cancer

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Synergism between anti-HER2 monoclonal antibody (trastuzumab) and paclitaxel has been shown in vitro and in vivo. In previous experiences, weekly administration of trastuzumab and paclitaxel has shown significant activity in metastatic breast cancer. In this phase II study, we evaluated the activity and the toxicity of this weekly regimen in anthracycline-and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. Between November 1999 and July 2001, 25 patients were treated with trastuzumab (4 mg kg À1 i.v. loading dose followed by 2 mg kg À1 i.v. week À1 ) and paclitaxel (60 -90 mg m À2 h À1 i.v. infusion week À1 ). The treatment was planned to continue until disease progression or prohibitive toxicity; in patients with responsive or stable disease, after 6 months of therapy, the decision to stop paclitaxel while continuing weekly trastuzumab was left to the physicians' judgement. At the median follow-up of 19.6 months (range 9.2 -38.1), all patients are evaluable for response and toxicity. We obtained four (16%) complete responses (CR), 10 (40%) partial responses (PR), four (16%) stable diseases and seven (28%) disease progressions. The response rate (CR þ PR) was 56% (95% CI, 36.5 -75.5%). The median duration of response was 10.4 months (range 4.1 -24.2 þ ). Median time to progression was 8.6 months (range 2.5 -24.2 þ ). The toxicity was mild; five patients experienced fever and chills during the first infusion of trastuzumab (20%); leukopenia grade 2 was recorded in one patient (4%). Two patients (8%) came off study for grade 3 cardiotoxicity (after 9 and 17 weeks of treatment, respectively): both had already received anthracyclines and taxanes. Onycholysis grade 2 was observed in five patients (20%). These results confirm that weekly administration of trastuzumab and paclitaxel is active in anthracycline-and taxane-pretreated metastatic breast cancer patients HER2-overexpressing. Since cardiac disfunctions grade 3 were observed (8%), we recommend that cardiac function should be monitored in these patients.

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Section: Discussionmentioning

confidence: 99%

Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer

Gori¹,

Colozza²,

Mosconi³

et al. 2004

Br J Cancer

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“…The HER2-positive tumors are now often treated with humanized monoclonal antibody to HER2 protein called trastuzumab in adjuvant, neoadjuvant and metastatic settings. Although, the therapy with trastuzumab is effective, it is not without serious cardiotoxicity in some patients 3,4 and is very expensive (approximately $50 000-60 000 for 1 year). However, triple-negative breast cancers lack any specific targeted therapy at the current time.…”

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confidence: 99%

Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation

et al. 2010

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Androgens exert growth inhibitory effects on estrogen receptor and progesterone receptor-negative breast cancer cell lines that show androgen receptor expression. These laboratory findings may be translated into inexpensive alternative therapies for hormone receptor-negative invasive breast cancers. Our aim was to systematically evaluate androgen receptor expression by immunohistochemistry in invasive breast cancers. Androgen receptor (clone AR441, Dako) expression was analyzed on 189 well-characterized consecutive invasive breast carcinomas represented with threefold redundancy on tissue microarrays. Androgen receptor expression was semi-quantitated using a histochemical score-like method and a score 410 was considered positive. Of the 189 consecutive invasive breast cancers, 151 (80%) were positive and 38 (20%) were negative for androgen receptor. The majority (95%) of estrogen receptor-positive tumors were also androgen receptor positive. Of the estrogen receptor-negative tumors, androgen receptor reactivity was seen in 3 of 30 (10%) triple-negative cases and in 5/8 (63%) estrogen receptor-negative/progesterone receptor-negative/HER2 þ cases. Six of eight estrogen receptor-negative/androgen receptor-positive cases showed apocrine differentiation. Androgen receptor expression in estrogen receptor-positive cases was associated with smaller tumor size (P ¼ 0.0001), lower Nottingham grade (P ¼ 0.002) and less frequent tumor cell necrosis (P ¼ 0.0001). Androgen receptor expression in estrogen receptor-negative tumors was associated with lower Nottingham grade (P ¼ 0.005) and apocrine differentiation (P ¼ 0.039). In conclusion, most estrogen receptor-positive breast tumors also express androgen receptor. Androgen receptor expression in estrogen receptor-negative/ progesterone receptor-negative/HER2 þ tumors (which commonly show apocrine differentiation) and a subset of triple -negative apocrine tumors suggest that these tumors together comprises the 'molecular apocrine' group described previously. However, these findings should be further confirmed on larger series of triplenegative and estrogen negative/progesterone negative/HER2 þ tumors. Androgen receptor-targeted therapy in estrogen/progesterone receptor-negative tumors may provide an inexpensive alternative to usual high-dose chemotherapy with or without trastuzumab. Keywords: androgen receptor; breast carcinoma; apocrine differentiation Breast cancer represents a diverse group of tumors that vary in clinical behavior and response to therapy. Currently, invasive breast cancer is treated by multi-modality therapy. Approximately 75% of breast cancers are positive for estrogen (ER) and/or progesterone (PR) receptor protein expression. This group of tumors is generally responsive to selective estrogen receptor modulators, 1 with relative resistance seen in a subset of tumors co-expressing HER2. 2 The remaining 20-25% of breast cancers are ER and PR negative and are not amenable to selective estrogen receptor modulators. This hormone receptor-negative group include...

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“…The incidence of cardiac adverse events associated with isolated use of trastuzumab ranges from 2 to 4% 1,3,5,7 ; and may increase up to 16% with previous use of anthracycline and/or cyclophosphamide 1,[3][4][5][6][7] . Trastuzumab has been administered in combination with placlitaxel to treat women who have not previously received CT for metastatic breast cancer 8 . Asymptomatic arrhythmias occur in association with the use of paclitaxel, and more severe cardiac adverse effects are related to CT schedules containing anthracyclines 1,3,6,9 .…”

Section: Se Reporta Un Caso De Cardiotoxicidad Asociada Con Quimiotermentioning

confidence: 99%

Reversible cardiotoxicity in a 54-year-old woman treated with trastuzumab

Martins¹,

Santos

Teles³

et al. 2012

Rev. méd. Chile

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Trastuzumab‐associated cardiotoxicity

Cited by 320 publications

References 33 publications

Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer

Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer

Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation

Reversible cardiotoxicity in a 54-year-old woman treated with trastuzumab

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