how come it took so long 2 discover that it may be the DCIS that expresses her2 that

[Lani]

tends to go onto invade???

In DCIS, HER2 Status May Predict Development of Invasive Breast Cancer


May 28, 2009 — Cases of ductal carcinoma in situ (DCIS) that overexpress the protein HER2/neu are much more likely to develop into invasive breast cancer than DCIS without the overexpression, according to a new study.

Analyzing biopsies of 106 women diagnosed with DCIS, researchers from the University of Pennsylvania found that 37% of the women had DCIS that overexpressed HER2 and that the likelihood a woman with DCIS had early invasive disease was 6.4-fold higher when a tumor overexpressed HER2.

The study appears in the May issue of Cancer Epidemiology, Biomarkers & Prevention.

Not all DCIS is the same.
"Not all DCIS is the same," said study senior author Brian Czerniecki, MD, PhD, codirector of the Rena Rowan Breast Center at the University of Pennsylvania in Philadelphia, in a press statement.

He explained that the patients in the study were not followed over time, but instead were analyzed at a single point in time after a diagnosis of DCIS.

"We merely asked, in a group of patients with clinical presentation of DCIS, how often and what predicts whether you see early invasive cancer develop," Dr. Czerniecki told Medscape Oncology.

Dr. Czerniecki illustrated 1 potential affect of the findings: "From a practical standpoint, if you know that a patient has a greater chance of invasive cancer when you're doing a lumpectomy or mastectomy, then you might want to do a sentinel node biopsy, because there is a greater chance the cancer has spread to the lymph nodes," he said.

However, the study needs to be validated by additional investigation, write Dr. Czerniecki and his coauthors.

Nevertheless, the authors suggest that targeting of HER2 in an early disease setting may forestall or prevent disease progression. "If HER2 is associated with invasion or plays a role in the development of invasive disease, then maybe targeting it early can keep people from moving from DCIS to invasive cancer," said Dr. Czerniecki.

Study Details

In this study of women who were diagnosed with DCIS between 2003 and 2007 at the University of Pennsylvania, the mean patient age was 53.4 years. Their biopsy specimens were diagnosed either by core needle biopsy or by needle localization biopsy, and were subjected to immunohistochemical staining for HER2, estrogen-receptor (ER), and progesterone-receptor (PR) expression.

Lesions were characterized as luminal A (ER positive or PR positive, HER2 negative), luminal B (ER positive or PR positive, HER2 positive), HER2 positive (ER negative and PR negative, HER2 positive), or basal-like (ER egative, PR negative, and HER2 negative).

Luminal A was the most common tumor phenotype and accounted for the most lesions (59%), and basal-like accounted for the fewest (3%).

The HER2-positive phenotypes — HER2 positive and luminal B — accounted for 21% and 17% of lesions, respectively.

Invasive disease was seen in HER2-positive DCIS in 8 of 23 cases (35%) and in luminal B DCIS in 7 of 17 cases (41%).

The DCIS specimens were also characterized by nuclear grade (high, intermediate, or low), assessed for the presence of comedo necrosis, and measured for tumor size.

Univariate analysis revealed significant associations between invasion and high nuclear grade, HER2 overexpression, and tumor size of more than 3 cm. However, of these associations, only tumors with HER2 overexpression remained significant upon multivariate analysis. DCIS lesions that overexpressed HER2 were more than 6 times as likely to be associated with invasive disease than were DCIS lesions in which HER2 overexpression was not present (odds ratio, 6.4; P = .01), write the authors.

HER2 expression may reflect an important pathway through which DCIS lesions may progress toward invasion.
The study is not the first to identify factors that predict the presence of invasive disease in patients diagnosed with DCIS, but few studies have looked at HER2 status. Nevertheless, among those that did, the findings echoed the current study's, suggest the authors. "The clustering of invasive foci in patients with HER2-overexpressing tumors suggests a disease pattern hinted at in other studies; specifically, HER2 expression may reflect an important pathway through which DCIS lesions may progress toward invasion," they write.

HER2 Expression May Be Fleeting

The authors note that there is a low frequency of HER2 expression in advanced disease and a higher frequency in early disease.

Given the results of their study, the authors speculate about the possible reason for these differing frequencies. "HER2 expression may be characteristic of tumors at a discreet stage of pathogenesis and may represent a transient phenomenon. Specifically, HER2 may be upregulated as in situ tumors progress to invasive disease and downregulated again in more advanced tumors," they write.

The researchers have disclosed no relevant financial relationships.

Cancer Epidemiol Biomarkers Prev. 2009;18:1386-1389. Abstract

If proven, strong implications for the use of herceptin,tykerb to prevent invasion ???but for how long???--implications for the success of Genentech so I hope they look into it soon!

[Laurel]

Thanks, Lani. Does seem like a bit of a "duh" to me, too!

[alicem]

When I got the pathology report from my biopsy I tried my best to understand it and had the surgeon explain everything. After showing I was ER + and PR +, it was blank next to the Her2 category. I asked the doctor what that was and he replied, "Oh, they only test for Her2 if you have a tumor, not if it is DCIS". I have always wondered about this. If I would have known I was Her2+ before my mastectomy then perhaps I would have had both breasts removed instead of just the one. I hate having something to potentially second guess myself about.