Familial breast cancer: Genetic counseling over time, including patients´ expectations and initiators considering the Angelina Jolie effect

<div><p>Purpose</p><p>The German Consortium for hereditary breast/ovarian cancer (GC-HBOC) aims for nationwide access to professional, individualized yet structured care for families at high risk. The identification of such families remains key for optimal care. Our study evaluates counselees’ characteristics, referral practices, expectations and motivations in respect to their first genetic consultation. The impact of the Angelina Jolie Effect (AJE) was prospectively assessed.</p><p>Methods</p><p>All counselees could participate through a questionnaire. Groups were built in respect to neoadjuvant chemotherapy (FT) and before/after AJE.</p><p>Results</p><p>The 917 (88.5%) counselees (FT: 8.2%) were on average female (97.3%), with a mean age of 44.6, had children (71.9%), higher education (88%), personal (46.4%) or at least one first-degree relative (74.6%) with BC/OC or known <i>BRCA1</i>/2 mutation (11.8%), were in a relationship (76.1%), and living in a village (40.7%). The AJE is associated with significantly fewer cancelations (p = 0.005), more attendance among men (4.2% vs. 0.8%, p = 0.002), and people with familial <i>BRCA1/2</i> (14.8% vs. 7.5%, p = 0.003). The majority seek information regarding their cancer risk (83%) or relatives’ risk (74.8%), HBOC (69.1%), and surveillance programs for themselves (66.6%) or relatives (60.6%).</p><p>Conclusion</p><p>Enhanced media awareness of genetic cancer motivates patients, including other patient groups. A higher number of participants, including more men, are attending GC due to the AJE. In terms of the rising complexity of genetic testing, the analysis of patients’ expectations and initiators for GC suggests that there is an urgent need to develop to participate motivation analysis. The factors revealed as impediments to accessing GC-HBOC guide recommendations to optimize access to genetic counseling. Medical educational programs for primary gynecologists and families at risk might be options to reach more participants.</p></div

Characteristics of NFT counselees and influence of the “Angelina Jolie (AJ) effect” on them (“before AJ” and “after AJ” subgroups).

<p>Characteristics of NFT counselees and influence of the “Angelina Jolie (AJ) effect” on them (“before AJ” and “after AJ” subgroups).</p

Study participants.

<p>Study participants.</p

Socio-demographic data of the entire study population (NFT and FT).

<p>Characteristics of all counselees and differences between the NFT and FT groups.</p

Motivation groups for NFT counselees before and after AJ.

<p>Motivation groups for NFT counselees before and after AJ.</p

Expectations of NFT counselees.

<p>Counselees quantified different expectations and motivational factors for visiting the Center for HBOC using a scale that ranged from 0 (motivation factor does not apply) to 4 (motivation factor applies completely).</p

Initiator groups for genetic counseling.

<p>Referral by <b>a)</b> medical professionals/physicians and <b>b)</b> Heidelberg University Hospital in the NFT and FT groups and the NFT subgroups “before AJ” and “after AJ”.</p

Cell nucleus areas of 14 pairs of healthy and varicose GSV samples.

<p>Cell nucleus areas of 14 pairs of healthy and varicose GSV samples.</p

Expression of relaxin-2 and its receptor RXFP1 in surgical samples of healthy and varicose GSV, and pharmacological stimulation.

<p>(A) Relaxin-2 content is decreased in varicose compared to healthy GSV, determined by ELISA (9.12±3.39 pg/mg versus 12.49±0.66 pg/mg of total protein; p = 0.01; Student's T-test). (B) Western Blot detection of RXFP1 in healthy and varicose GSV. RXFP1 bands are less pronounced in the varicose GSV samples. (C) In vitro pharmacology of surgical samples of GSV. Pulse-stimulations with KCl (kaliumchloride), arterenol (norepinephrinehydrochloride) and carbachol (carbamylcholine) induce contractions of the GSV specimens; relaxin-2 relaxes the specimens. The first KCl contraction was defined as 100% maximum contraction. Arterenol: 76%, carbachol: 51%, relaxin-2: −34% of maximum KCl contraction. (D) Constant perfusion with relaxin-2 partly antagonizes the contractions induced by pulse-stimulations with arterenol and carbachol: Arterenol: 76 to 47% (reduction of 29% of KCl maximum concentration), carbachol: 51 to 23% (reduction of 28% of KCl maximum concentration.</p

MiRNA levels in benign and malignant breast tissue.

<p>Levels of miR-127-3p, miR-376a and miR-652 are decreased in malignant primary breast cancer when compared to benign breast tissue. Box and whisker plots show RNU6B normalized relative miRNA levels for miR-127-3p and miR-652. As an exception un-normalized Ct values are presented for miR-376a as the normalization strategy was not applicable for this particular miRNA (due to the rather low miR-376a levels in the investigated tissue samples). A two-tailed P<0.05 was considered significant (Wilcoxon rank sum test).</p