Is uterine serous carcinoma a part of hereditary breast cancer syndrome?

5587 Background: Whilst the association between breast cancer and uterine serous carcinoma (USC) is attributed to tamoxifen treatment, few studies have reported that this increased risk is independent of tamoxifen. Methods: To further investigate the relationship between breast cancer and USC, we retrospectively studied 216 patients from 5 hospital trusts in Birmingham, UK who were diagnosed with USC between 1993 and 2012. We collected personal history of cancer in these cases before or after USC diagnosis. In addition FIGO staging, clinical and survival data were collected from our local cancer registry and patients’ clinical records. Results: In this case series, 56 patients (25.9%) had personal history of at least one cancer before and 18 patients (8.3%) had history of at least one cancer after the diagnosis of USC. Within the group of patients with the history of cancer before the USC, 38 patients (68%, 17.5% of all cases) had personal history of breast cancer prior to the development of USC, higher than the UK expected age standardised relative incidence of breast cancer (350 in 100,000, CRUK 2006-2008). Although 27/38 cases (71%) had endocrine treatment for their primary breast cancer, 11/38 patients (29%) did not have any tamoxifen treatment due to hormone receptor negative breast cancer. Additionally the median age of breast cancer diagnosis for the hormone receptor negative group was significantly lower than those patients who had hormonal treatment for their breast cancer (56 vs. 64 years, p :0.036) compatible with the younger age at diagnosis expected of the familial (BRCA mutated) or triple negative breast cancer. Of 18 patients with a second cancer after diagnosis of USC, 6 patients (33%) were diagnosed with breast/ovarian cancer. This group also had no treatment with tamoxifen. Conclusions: Lack of exposure to tamoxifen and younger age at diagnosis in this subgroup suggest that other factors such as a common underlying genetic predisposition may be responsible for the development of both malignancies. We propose that at least a subgroup of USC may be a part of hereditary breast cancer syndrome. This may have implications in prevention (prophylactic hysterectomy) or trials of targeted treatments (PARP inhibitors) for a subgroup of USC patients.

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Uterine serous carcinoma: key advances and novel treatment approaches

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-002753 ◽

2021 ◽

pp. ijgc-2021-002753

Author(s):

J Stuart Ferriss ◽

Britt K Erickson ◽

Ie-Ming Shih ◽

Amanda N Fader

Keyword(s):

Endometrial Cancer ◽

Black Women ◽

Treatment Options ◽

Molecular Genetic ◽

Serous Carcinoma ◽

Cancer Syndrome ◽

Her2 Positive ◽

Incidence And Mortality ◽

History Of ◽

Uterine Serous Carcinoma

The incidence and mortality rates from endometrial cancer continue to increase worldwide, while rates in most other cancers have either plateaued or declined considerably. Uterine serous carcinoma represents a fraction of all endometrial malignancies each year, yet this histology is responsible for nearly 40% of all endometrial cancer-related deaths. These deaths disproportionately affect black women, who have higher rates of advanced disease at diagnosis. Molecular genetic analyses reveal major alterations including TP53 mutation, PIK3CA mutation/amplification, ERBB2 amplification, CCNE1 amplification, FBXW7 mutation/deletion, PPP2R1A mutation, and somatic mutations involving homologous recombination genes. Clinical risk factors for uterine serous carcinoma include advancing age, a history of breast cancer, tamoxifen usage, and the hereditary breast–ovarian cancer syndrome. Surgery remains the cornerstone of treatment. Recent advances in our understanding of uterine serous carcinoma molecular drivers have led to development of targeted therapeutics that promise improved outcomes for patients. Overexpression or amplification of HER2 in uterine serous carcinoma carries a poor prognosis; yet this actionable target has led to the incorporation of several anti-HER2 therapies, including trastuzumab which, when added to conventional chemotherapy, is associated with improved survival for women with advanced and recurrent HER2-positive disease. The combination of pembrolizumab and lenvatinib is also a promising targeted treatment strategy for women with uterine serous carcinoma, with a recent phase II study suggesting a 50% response rate in women with recurrent disease. Several trials examining additional targeted agents are ongoing. Despite years of stalled progress, meaningful, tailored treatment options are emerging for patients with this uncommon and biologically aggressive endometrial cancer subtype.

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Clinical Characteristics Affect the Impact of an Uninformative DNA Test Result: The Course of Worry and Distress Experienced by Women Who Apply for Genetic Testing for Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.03.7259 ◽

2006 ◽

Vol 24 (22) ◽

pp. 3672-3677 ◽

Cited By ~ 61

Author(s):

Sandra van Dijk ◽

Daniëlle R.M. Timmermans ◽

Hanne Meijers-Heijboer ◽

Aad Tibben ◽

Christi J. van Asperen ◽

...

Keyword(s):

Breast Cancer ◽

Brca Mutation ◽

Personal History ◽

True Negative ◽

Dna Test ◽

Dna Mutation ◽

Clinical Variables ◽

History Of ◽

Test Result ◽

History Of Cancer

Purpose DNA mutation testing for breast cancer usually yields an uninformative result, which is a negative result in the absence of a known BRCA mutation within the family. However, few data are available on the psychological impact of this result. Moreover, the clinical heterogeneity within this group has not yet been considered. This study provides prospective data about the course of cancer-specific worry and distress for different groups of test applicants. Patients and Methods All DNA test applicants (n = 238) completed three questionnaires: before and 1 and 7 months after disclosure of a DNA mutation test. With repeated-measures analysis of variance, differences were assessed between BRCA1/2-positive women (n = 42), BRCA1/2–true-negative women (n = 43), and women with an uninformative test result (n = 153). Results On the group level, women with an uninformative result seemed to be reassured after disclosure (P < .001), but to a lesser extent than those women who received a true-negative result. However, not all women with an uninformative result reacted similarly: higher levels of worry and distress could be explained by relatively straightforward clinical variables, namely a personal history of cancer (P ≤ .001) and a higher pedigree-based risk (P ≤ .005). Furthermore, these clinical variables determined whether these women were either comparable to women who received a true-negative result or to BRCA mutation carriers. Conclusion Women with an uninformative result form a heterogeneous group of test applicants. The subpopulation of those with both a personal history of cancer and a relatively high pedigree-based risk expressed the highest levels of worry 7 months after DNA testing.

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103P Rate of BRCA1/2 pathogenic variants according to family and personal history of cancer in a large cohort of triple-negative breast cancer (TNBC) patients (pts) younger than 60 years of age

Annals of Oncology ◽

10.1016/j.annonc.2021.08.383 ◽

2021 ◽

Vol 32 ◽

pp. S400-S401

Author(s):

S. Zovato ◽

G. Griguolo ◽

S. Agata ◽

S. Tognazzo ◽

M.V. Dieci ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Large Cohort ◽

Personal History ◽

Pathogenic Variants ◽

History Of ◽

History Of Cancer

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Family history of cancer associated with improved survival in uterine serous carcinoma

Gynecologic Oncology ◽

10.1016/j.ygyno.2019.03.219 ◽

2019 ◽

Vol 154 (1) ◽

pp. e25

Author(s):

L.H. Palavalli Parsons ◽

S.R. Pierce ◽

P.A. Gehrig ◽

J.S. Lea

Keyword(s):

Family History ◽

Serous Carcinoma ◽

Family History Of Cancer ◽

History Of ◽

Uterine Serous Carcinoma ◽

History Of Cancer

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Personal history of breast cancer as a significant risk factor for endometrial serous carcinoma in women aged 55 years old or younger

International Journal of Cancer ◽

10.1002/ijc.25395 ◽

2010 ◽

Vol 128 (4) ◽

pp. 763-770 ◽

Cited By ~ 18

Author(s):

Sharon X. Liang ◽

Micheal Pearl ◽

Shu Liang ◽

Li Xiang ◽

Lin Jia ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factor ◽

Significant Risk ◽

Significant Risk Factor ◽

Personal History ◽

Serous Carcinoma ◽

History Of

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Faculty Opinions recommendation of Accuracy and outcomes of screening mammography in women with a personal history of early-stage breast cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.8814959.9348058 ◽

2011 ◽

Author(s):

Gretchen Kimmick

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Screening Mammography ◽

Personal History ◽

Early Stage Breast Cancer ◽

History Of

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Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200107000-00003 ◽

2001 ◽

Vol 11 (4) ◽

pp. 272-276 ◽

Cited By ~ 1

Author(s):

N. Nishimura ◽

T. Hachisuga ◽

T. Saito ◽

T. Kawarabayashi

Keyword(s):

Breast Cancer ◽

Endometrial Carcinoma ◽

Cancer Patients ◽

Myometrial Invasion ◽

Tamoxifen Treatment ◽

Adjuvant Tamoxifen ◽

Serous Carcinoma ◽

Breast Cancer Patients ◽

Two Stage ◽

Endometrial Carcinomas

Abstract.Nishimura N, Hachisuga T, Saito T, Kawarabayashi T. Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients.This study aimed to detail the clinicopathologic features of endometrial carcinomas that developed in Japanese patients receiving adjuvant tamoxifen treatment for breast cancer patients. Ten endometrial carcinomas in tamoxifen-treated breast cancer patients were collected from two medical centers. The endometrial carcinomas included two stage Ia, four stage Ib, two stage Ic and two stage IIIc. Three tumors were Grade 1, six were Grade 2, and one was Grade 3. The tumor was limited to the endometrium in two cases. Myometrial invasion was limited to the inner half of the myometrium in five cases and involved the outer half in three. A mild degree of lymphovascular space invasion was identified in five cases. Deep cervical invasion was recognized in one case. The cell types comprised nine endometrioid adenocarcinomas and one serous carcinoma. Five of eight postmenopausal endometrial carcinomas were associated with polypoid endometrial lesions composed of cystically dilated atrophic and proliferative glands widely separated by fibrotic stroma. Two patients with retroperitoneal lymph node metastases died of endometrial cancer. One patient developed a contralateral breast cancer during tamoxifen treatment. No patient died of breast cancer. We did not demonstrate a higher frequency of either high-grade tumors or unfavorable histologic subtypes in tamoxifen-treated Japanese breast cancer patients.

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