Wednesday, May 27, 2009

Management of Breast Cancer in the BRCA positive population

Patrick (MSII) presents on the Management of BRCA positive patients.

Case: 30 yo AAF with a mass in the UIQ of the R breast. Maternal aunt with Breast CA at 44, also paternal grandmother with breast cancer and ovarian cancer at 86.

Biopsy: Poorly differentiated 1.3cm cancer. Triple negative. Lumpectomy and SLNB negative. (T1N0M0 triple negative). BRCA1 positive.

BRCA1: 17q21 activated by DNA damage. Interacts with CHK1 and CHK2
BRCA2: 13q12 regulates cell cycle, promotes S/G2 arrest

BRCA mutations in 1%
Enriched in the Ashkenazi Jewish population (Icelandic, Swedish, Hungarian populations as well).

Criteria for testing: Early breast cancer <=50. Two primaries in a single individual or close relative. Breast and ovarian primaries. Family member with male breast cancer.

Testing costs 300-3000$ depending on the extent of the test.

Breast Cancer 65-85% 45-85%
Ovarian Cancer 37-62% 11-23%
high grade low grade
triple negative er/pr + her2-

Early Screening. Self Breast exams at 18, clinical exams at 25. Mammograms and MRI testing at 25 or 10 years before the youngest age a relative was diagnosed with breast cancer.

Breast MRI Kriege NEJM 351:427. 1909 high risk patients (358 BRCA carriers), MRI sensitivity 80%, spec 90%, Mammo sens 33%, spec 95%.

Warner JAMA. 236 carriers. MRI sens 77%, spec 95.4%. Also looked at mammo, U/S, and CBE.

Meijers NEJM 2001;345:159. 139 carriers, 76 underwent prophylactic mastectomy, the rest choosing surveillance. With f/u of 3 years. 0/76 cancers in the mastectomy group. 8/63 in the the surveillance group, p=0.003. 5yr incidence in the surveillance group was 17%.

PROSE JCO 2004 22:1055. 90% reduction in breast cancer in carriers. In patients who also had a BSO, there was a 95% reduction.

Kauff: Prospective prophylactic bilateral salpingo-oophorectomy (BSO), HR of 0.25 for the development of ovarian or breast cancers.

Eisen: JCO 23:7491 - BSO conferred a 46-56% reduction in breast cancers. Benefit was greater if performed before 40 years of age.

Domcheck Lancet Onc 7:233. 426 with some getting BSO, some observation (prospective cohort). Overall Survival HR was 0.24 (SS) with BSO.

Pierce 160 BRCA carriers undergoing BCT. Incidence of contralateral cancers was in carriers 39%, vs 7% controls, p<0.001 at 15years. Pierce also reports in the JCO 2000, that there was no clear survival detriment to breast consevation (BCT) in carriers (though follow up was only 5 years).

Case resolution: Pt consuled about prophylactic mastectomy, BCT, prophylactic BSO, and TC chemotherapy. Pt elected to pursue BCT with close followup, with BSO after child bearing in complete (preferably before age 40).

Tuesday, May 5, 2009

Oncoanatomy: Mediastinum

AC presents the resident portion of the Oncoanatomy module on the Mediastinum

Anterior, middle and posterior mediastinal compartments have no intrinsic discriminating planes, however the division is useful for differential diagnosis. Primarily the middle compartment contains the heart, great vessels and airways, the anterior and posterior compartments are simply in front of or behind these structures.

Anterior Compartment
Contents include Internal mammary vessels, thymus, fat pad.
DDx for masses: 4Ts - Thymic lesions, Thyroid, Teratoma, (Terrible) Lymphoma PMBCL or Lymphoblastic lymphoma

Primary mediastinal b-cell lymphoma - variant of DLBCL. R-CHOP often used. Consolidative RT is often used. Outcomes may be more favorable than other variants of DLBCL. Peak age in the 30s and 40s.

Lymphoblastic Lymphoma: Pre B or C cells, blurred line between this and lyphoblastic lymphoma. Male predominance, peak incidence in 2nd and 3rd decades. Thymic origin CD7+, CD5+, CD2+. Mediastinal involvement in 60-70%. Treated along leukemic protocols (VPDC). Role of RT is unclear. In T-cell cases, CNS prophylaxis is indicated (intrathecal MTX +/- cranial RT).

Middle Mediastinum: Great vessels, Heart, Trachea and Airways.
Primarily metastasis or lyphoma.

Posterior Mediastinum: Esophagus, Lymph nodes, Fat, Sympathetic chains, the Azygous vein, Thoracic duct.
DDx: Neurogenic tumors, esophageal tumors, aortic lesions.

Hodgkin Lymphoma. Historically treated with RT alone with a 5yr survival of approximately 30%.

Mantle field: superior edge is at the mastoid tips, inferior at T9-10 spaces, lateral borders include the axillary nodal regions. Custom blocking is used for bilateral lungs, and humeral heads, shaped to include the bilateral hila. Lanrynx block is placed around 20Gy.

JAMA 2003;290:2831 (Hull) - 415pts with HL treated with RT or CTRT, with 80% recieving mantle fields. 10% developed CAD by 20 years. 6% had valvular dysfunction at 22yrs.

RT + doxorubicin. Myrehaug, Leukemia Lymphoma 49:1486. Doxorubicin seems to have a supra additive effect on cardiac toxicity with an HR for cardiac morbidity of 2.77 vs HR 1.82 with RT alone.