Improved Prognosis by Trastuzumab of Women With HER2-Positive Breast Cancer Compared
 

Improved Prognosis by Trastuzumab
of Women With HER2-Positive Breast
Cancer Compared With Those With
HER2-Negative Disease



TO THE EDITOR: We have read with great interest the article by
Dawood et al,1 and we think that the findings reported by the authors
deserve some comments.

Between June 2000 and January 2004, we consecutively enrolled
68 women with metastatic breast cancer: 33 patients received
vinorelbine alone, while 35 patients were given trastuzumab plus
vinorelbine according to human epidermal growth factor receptor-2
(HER2) expression determined by immunohistochemistry.2 This was
formally a phase II study, which demonstrated that women with
HER2-overexpressing metastatic breast cancer when treated with trastuzumab
and vinorelbine had a better prognosis than those with
HER2-negative disease treated with vinorelbine alone.

In our study, the vast majority of patients received chemotherapy
for metastatic disease. No one had previously received
vinorelbine and only three women with HER2-positive disease had
previously received trastuzumab for metastatic disease. Thus, by our
findings,2 we provocatively suggested that the assumption that HER2-
positive tumors have a worse prognosis could be no longer valid when
treated with trastuzumab. In fact, with the use of trastuzumab,women
with HER2-positive disease appeared to do far better than did patients
with HER2-negative tumors, exhibiting consistently higher rates of
response, longer time to progression, and improved overall survival.

Given that HER2-positive breast cancer is being treated as a
distinct clinical entity, we cannot include women with HER2-positive
breast cancer in trials recruiting patients regardless of HER2 status.
Our study2 was criticized because it lacked a randomization plan. But,
because in HER2-positive tumors chemotherapy alone as first-line
treatment has been replaced with a combination of chemotherapy and
trastuzumab,3-5 a trial without trastuzumab inHER2-positive patients
with breast cancer would be ethically inappropriate. Thus, a prospective
comparison between patients treated for HER2-positive disease
and women treated for HER2-negative breast cancer can be formally
performed only as a phase II study, in which consecutively enrolled
patients with metastatic breast cancer are treated with chemotherapy
with or without trastuzumab, according to HER2 status.

Decades of randomized clinical trials on the first-line treatment
of metastatic breast cancer have never been able to show so
remarkable differences in time to progression and overall survival
as the three fundamental randomized trials comparing chemotherapy
with chemotherapy plus trastuzumab in women with HER2-
overexpressing metastatic breast cancer3-5 have been able to do. The
merit of the study by Dawood et al1 is to have retrospectively compared
the prognosis of three groups of patients: women with metastatic
HER2-positive breast cancer with and without the addition
of trastuzumab with women with HER2-negative disease.Weagree
with the authors1 that trastuzumab has not only beneficially
changed the natural history of HER2-positive breast cancer, but it
has also improved the prognostic outcomes of women with HER2-
overexpressing tumors beyond those of women with HER2-
negative disease.

Gianluigi Ferretti, Alessandra Fabi, Alessandra Felici,
and Paola Papaldo
Regina Elena Cancer Institute, Rome, Italy

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.

REFERENCES
1. Dawood S, Broglio K, Buzdar AU, et al: Prognosis of women with metastatic
breast cancer by HER2 status and trastuzumab treatment: An institutional-based
review. J Clin Oncol 28:92-98, 2010
2. Papaldo P, Fabi A, Ferretti G, et al: A phase II study on metastatic breast
cancer patients treated with weekly vinorelbine with or without trastuzumab
according to HER2 expression: Changing the natural history of HER2-positive
disease. Ann Oncol 17:630-636, 2006
3. Slamon DJ, Leyland-Jones B, Shak S, et al: Use of chemotherapy plus a
monoclonal antibody against HER2 for metastatic breast cancer that overexpresses
HER2. N Engl J Med 344:783-792, 2001
4. Gasparini G, Gion M, Mariani L, et al: Randomized phase II trial of weekly
paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of
patients with Her-2 positive advanced breast cancer. Breast Cancer Res Treat
101:355-365, 2007
5. Marty M, Cognetti F, Maraninchi D, et al: Randomized phase II trial of the
efficacy and safety of trastuzumab combined with docetaxel in patients with
human epidermal growth factor receptor 2-positive metastatic breast cancer
administered as first-line treatment: The M77001 study group. J Clin Oncol
23:4265-4274, 2005
DOI: 10.1200/JCO.2010.28.2525; published online ahead of print at
www.jco.org on May 17, 2010





www.jco.org on May 17, 2010

Re: Improved Prognosis by Trastuzumab of Women With HER2-Positive Breast Cancer Compa
 

Thanks Barbara for posting this information. I hope we will see continued improvements as more targeted treatments become available.
Ellie

Re: Improved Prognosis by Trastuzumab of Women With HER2-Positive Breast Cancer Compa
 

Thank you, Barbara, for the article. Glad to hear some good news.

Amelia

Re: Improved Prognosis by Trastuzumab of Women With HER2-Positive Breast Cancer Compa
 

Thank you.
It gives me more power to care my wife

Re: Improved Prognosis by Trastuzumab of Women With HER2-Positive Breast Cancer Compa
 

Thanks Barbra, I don't have mets (thankfully!) but am so glad her2+ is getting some good press for once!:)