Genetics of Women With Lobular Carcinoma in Situ of the Breast

OBJECTIVES:

Primary

* Identify inherited variation that predisposes women to develop lobular carcinoma in situ (LCIS) of the breast.
* Identify the frequency of these variants and determine the effect they have on tumor risk.
* Determine how worthwhile it would be to test for these variants in the clinical setting so that those at higher risk could be identified, counseled, and screened.

Secondary

* Analysis of genetic changes within LCIS with the aim of identifying cases of LCIS which may progress to invasive cancer.

OUTLINE: Patients and control participants undergo blood collection. DNA is extracted from blood samples and used to genotype at selected polymorphisms, compare allele frequencies (used to associate alleles with disease) using a genome-wide single nucleotide polymorphism (SNP) screen. Archival tumor samples (if available) from patients are used for DNA-, RNA-, or protein-based analyses.

All participants complete a questionnaire about family history, a brief medical history, and provide epidemiological data to a genetic counselor. Participants identified to be at risk for known hereditary predisposition to cancer will be referred to a clinical genetics service. Individual results of this study are not disclosed to participants.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

PROJECTED ACCRUAL: A total of 2,000 participants (1,000 patients and 1,000 matched controls) will be accrued for this study.

• gene expression analysis (Genetic)
• molecular diagnostic method (Genetic)
• polymorphism analysis (Genetic)
• protein expression analysis (Genetic)
• medical chart review (Other)
• questionnaire administration (Other)

Primary outcomes

• Inherited variation predisposing development of lobular carcinoma in situ (LCIS) of the breast in women
• Frequency and effect of variants on tumor risk
• Clinical setting variant test value in identifying, counseling and screening those women at higher risk

Secondary outcomes

• LCIS genetic changes which may progress to invasive cancer

Sex: Female, ages: any to 60 Years, accepts healthy volunteers

DISEASE CHARACTERISTICS:

* Meets 1 of the following criteria:

  * Current or prior diagnosis of lobular carcinoma in situ (LCIS) of the breast, including any of the following cases:

    * Pure LCIS
    * LCIS with subsequent development of invasive breast cancer of any morphological subtype
    * LCIS presenting as an incidental finding together with invasive breast cancer of any morphological subtype
  * Control participant matched for age and ethnicity to each LCIS patient

    * Not affected by LCIS
    * No history of ductal carcinoma in situ of the breast
    * No breast cancer
    * No relative (up to 2nd degree) who has been affected by breast cancer
    * Male or female

PATIENT CHARACTERISTICS:

* Not specified

PRIOR CONCURRENT THERAPY:

* Not specified

• Elinor Sawyer, MD, Study chair, London Research Institute
• Rebecca Roylance, MD, Barts and the London School of Medicine and Dentistry