Elucidating Prognosis and Biology of Breast Cancer Arising in Young Women Using Gene Expression Profiling

Azim, Hatem A.; Michiels, Stefan; Bedard, Philippe L.; Singhal, Sandeep K.; Criscitiello, Carmen; Ignatiadis, Michail; Haibe‐Kains, Benjamin; Piccart, Martine; Sotiriou, Christos; Loi, Sherene

doi:10.1158/1078-0432.ccr-11-2599

Cited by 330 publications

(287 citation statements)

References 48 publications

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“…Luminal A cancer, with better prognosis, was detected in 35% of the older and 17% of the younger women [17]. However, it seems that worse tumor biology in patients with BC is not only connected with less beneficial distribution of particular molecular subtypes of cancer.…”

Section: Tumor Biologymentioning

confidence: 99%

Breast cancer in young women

Radecka¹,

Litwiniuk²

2016

Ginekol Pol

119

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Breast cancer (BC) in young women is rare, affecting only 4-6% of women under the age of 40. Regardless, BC remains the most common malignancy among younger patients. Recently, a significant increase in BC rates has been observed among pre-menopausal subjects. Breast cancer in young women requires special attention due to its specific morphologic and prognostic characteristics and unique aspects, including fertility preservation and psychosocial issues (e.g. its impact on family life and career). Young women are more likely to have tumors with higher incidence of negative clinicopathologic features (higher histological grade, more lymph node positivity, lower estrogen receptor (ER) positivity, higher rates of Her2/neu overexpression). Also, they tend to be diagnosed at more advanced stages of the disease. That, in turn, contributes to less favorable prognosis as compared to older women. Young women are generally treated similarly to older patients. Surgical management includes mastectomy or breast-conserving surgery, followed by radiation therapy (younger women have higher local recurrence rates than older women, especially after breast-conserving therapy). Although the basics of chemotherapy are the same for patients of all ages, younger women have some special considerations. It is important to consider options for fertility preservation before starting systemic treatment. Patients should have access to genetic testing as their results may affect the choice of therapy. Younger women and their families should receive adequate psychological support and counselling.

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Section: Tumor Biologymentioning

confidence: 99%

Breast cancer in young women

Radecka¹,

Litwiniuk²

2016

Ginekol Pol

119

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“…5 However, molecular studies have also suggested that breast cancer in young patients may be characterized by unique disease biology, as compared to older patients, beyond subtype distribution. 6 One of the predisposing factors for breast cancer is germline mutation in tumor suppressor genes such as BRCA1/2. In younger patients its frequency may be as high as 10.9 to 23%, as reported in women from different countries.…”

Section: Introductionmentioning

confidence: 99%

Somatic mutations in breast and serous ovarian cancer young patients: a systematic review and meta-analysis

Encinas

Maistro

Pasini

et al. 2015

Rev. Assoc. Med. Bras.

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Objective: our aim was to evaluate whether somatic mutations in five genes were associated with an early age at presentation of breast cancer (BC) or serous ovarian cancer (SOC). Methods: COSMIC database was searched for the five most frequent somatic mutations in BC and SOC. A systematic review of PubMed was performed. Young age for BC and SOC patients was set at ≤35 and ≤40 years, respectively. Age groups were also classified in <30years and every 10 years thereafter. Results: twenty six (1,980 patients, 111 younger) and 16 studies (598, 41 younger), were analyzed for BC and SOC, respectively. In BC, PIK3CA wild type tumor was associated with early onset, not confirmed in binary regression with estrogen receptor (ER) status. In HER2-negative tumors, there was increased frequency of PIK3CA somatic mutation in older age groups; in ER-positive tumors, there was a trend towards an increased frequency of PIK3CA somatic mutation in older age groups. TP53 somatic mutation was described in 20% of tumors from both younger and older patients; PTEN, CDH1 and GATA3 somatic mutation was investigated only in 16 patients and PTEN mutation was detected in one of them. In SOC, TP53 somatic mutation was rather common, detected in more than 50% of tumors, however, more frequently in older patients. Conclusion: frequency of somatic mutations in specific genes was not associated with early-onset breast cancer. Although very common in patients with serous ovarian cancer diagnosed at all ages, TP53 mutation was more frequently detected in older women.

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“…Breast cancer arising in young women exhibits distinct biological features and has been shown to pursue an aggressive clinical behavior (Cancello et al 2010, Azim et al 2012a, Collins et al 2012, Narod 2012. Among the unique situations that young women with breast cancer may face is pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Biology of breast cancer during pregnancy using genomic profiling

Azim

Brohée

Peccatori

et al. 2014

Endocrine Related Cancer

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Breast cancer during pregnancy is rare and is associated with relatively poor prognosis. No information is available on its biological features at the genomic level. Using a dataset of 54 pregnant and 113 non-pregnant breast cancer patients, we evaluated the pattern of hot spot somatic mutations and did transcriptomic profiling using Sequenom and Affymetrix respectively. We performed gene set enrichment analysis to evaluate the pathways associated with diagnosis during pregnancy. We also evaluated the expression of selected cancer-related genes in pregnant and non-pregnant patients and correlated the results with changes occurring in the normal breast using a pregnant murine model. We finally investigated aberrations associated with disease-free survival (DFS). No significant differences in mutations were observed. Of the total number of patients, 18.6% of pregnant and 23% of non-pregnant patients had a PIK3CA mutation. Around 30% of tumors were basal, with no differences in the distribution of breast cancer molecular subtypes between pregnant and non-pregnant patients. Two pathways were enriched in tumors diagnosed during pregnancy: the G protein-coupled receptor pathway and the serotonin receptor pathway (FDR !0.0001). Tumors diagnosed during pregnancy had higher expression of PD1 (PDCD1; PZ0.015), PDL1 (CD274; PZ0.014), and gene sets related to SRC (PZ0.004), IGF1 (PZ0.032), and b-catenin (PZ0.019). Their expression increased almost linearly throughout gestation when evaluated on the normal breast using a pregnant mouse model underscoring the potential effect of the

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Elucidating Prognosis and Biology of Breast Cancer Arising in Young Women Using Gene Expression Profiling

Cited by 330 publications

References 48 publications

Breast cancer in young women

Breast cancer in young women

Somatic mutations in breast and serous ovarian cancer young patients: a systematic review and meta-analysis

Biology of breast cancer during pregnancy using genomic profiling

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