Contralateral breast cancer (CBC) is the most common second primary cancer in patients diagnosed with breast cancer.1 Patients with a history of breast cancer have an increased risk of developing a second primary breast cancer (PBC), with an annual risk of 0.5% to 1% or a cumulative lifetime risk of 2% to 15%.2 Because breast cancer is the most commonly diagnosed cancer in women in the United States,3 prevention of CBC is a significant clinical issue. Analyses are underway to evaluate the relationship among radiotherapy, newer hormonal therapies, chemotherapy agents, and obesity in survivors. J Clin Oncol 2:: Kuukasjarvi T, Kononen J, Helin H, et al: Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy. Contact Us Increased intervention or post treatment surveillance … In this issue, Arpino et al6 conclude that the hormone receptor status of the PBC does not predict the hormone receptor status of a subsequent CBC in the absence of prior adjuvant therapy. ASCO Meetings Given these conclusions, should we consider prescribing tamoxifen to all patients with a diagnosis of PBC, regardless of receptor status, as a chemopreventive agent for CBC? JCO OP DAiS, ASCO eLearning A new method to elucidate the clonal relationship between tumors has been published inBreast Cancer Research. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS 313) and contralateral breast cancer (CBC) risk. This differentiation has implications for the development of drug resistance and subsequent systemic treatment of the CBC. In addition, the increased risk of thromboembolic disease and endometrial cancer associated with tamoxifen would need to be considered. However, if considered metastatic, systemic treatment alone in the form of hormonal or cytotoxic chemotherapy may be considered. J Clin Oncol 17:: Anderson WF, Chatterjee N, Ershler WB, et al: Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res Treat 76:: Armitage P, Doll R: The age distribution of cancer and a multi-stage theory of carcinogenesis. Contralateral axillary metastasis (CAM), posterior to a unilateral breast cancer, is a rare entity. Subscribers Contralateral breast cancer (CBC) is the most common second primary cancer in patients diagnosed with breast cancer.1Patients with a history of breast cancer have an increased risk of … The cumulative risk for contralateral breast cancer 25 years after first breast cancer was 47.4% (95% CI, 38.8% to 56.0%) for patients from families with BRCA1 or BRCA2 mutations. Natl Cancer Inst Monogr 68:: Adami HO, Bergstrom R, Hansen J: Age at first primary as a determinant of the incidence of bilateral breast cancer: Cumulative and relative risks in a population-based case-control study. Conquer Cancer Foundation Determining ER status by immunohistochemistry might have led to a more accurate measurement of ER status.11. The invasive status of the contralateral tumour diagnosis and tumour morphology was collected. Due to the high incidence of breast cancer and improving survival, an increasing number of breast cancer survivors are at risk of developing contralateral breast cancer (CBC). Cancer 55:: Jemal A, Murray T, Samuels A, et al: Cancer statistics, 2003. Patients treated with tamoxifen whose PBCs were ER positive were equally likely to develop an ER-positive or ER-negative CBC, which is consistent with the results from the National Surgical Adjuvant Breast and Bowel Project P-1 prevention study.9. Members of families with BRCA1 mutations had a 1.6-fold (95% CI, 1.2-fold to 2.3-fold) higher risk of contralateral breast cancer … The most common of these second cancers is contralateral breast cancer (CBC), which is estimated to occur at a rate of 0.5% per year (3–6). CA Cancer J Clin 53:: Robbins GF, Berg JW: Bilateral primary breast cancer: A prospective clinicopathological study. Trends Endocrinol Metab 15:: Clark GM, Osborne CK, McGuire WL: Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer. 4585-4587. However, whether the second tumor (second breast cancer (BC2)) … Before this can be accomplished, a more precise characterization and definition of CBC must be attained. Contralateral breast cancer (CBC) is today treated as a new primary tumor, independent of the first breast cancer (BC1). Contralateral breast cancer is the most common second cancer in women with primary breast cancer. J Clin Oncol 23:: Swain SM, Wilson JW, Mamounas EP, et al: Estrogen receptor status of primary breast cancer is predictive of estrogen receptor status of contralateral breast cancer. TAPUR Study, Terms of Use | Privacy Policy | Among patients receiving no adjuvant therapy, 88% who had an ER-positive PBC and 75% who had an ER-negative PBC developed an ER-positive CBC (P = .11). It is unlikely that the question of whether tamoxifen is beneficial for patients with an ER-negative PBC will ever be answered in a prospective clinical trial because of the low event rate requiring a large number of study patients. This compares to a median age of 47 years in a National Surgical Adjuvant Breast and Bowel Project study evaluating the ER status in PBC and CBC. The ER-positive rate (75% to 88%) in the CBC group of the current study is similar to the ER-positive rate (75.1%) of primary breast tumors seen in the general population from the Surveillance, Epidemiology, and End Results data.12 This high rate of ER-positive CBC in the absence of adjuvant therapy supports the hypothesis that the CBCs seen in the current study may be sporadic cancers unrelated to the PBC. Laboratory studies suggest that inhibition of the cyclooxygenase (COX)-2 enzymes inhibits breast cancer development. J Natl Cancer Inst 96:: 2318 Mill Road, Suite 800, Alexandria, VA 22314, © 2021 American Society of Clinical Oncology. With increasing cure rates comes increasing concern about their long-term health. However, there is also evidence supporting the emergence of ER-negative cancers from ER-positive precursors. The most common second cancer in breast cancer survivors is another breast cancer. Absolutely! Early observations by Paget16 resulted in the seed and soil theory, in which metastases develop only when particular cells with metastatic ability are present in the appropriate host microenvironment. In situ lesions (2%) made up a minority of the tumors in the patients in the study by Arpino et al6 because they were not routinely sent for hormone receptor assays. The authors of this model conclude that differing breast cancer phenotypes result from a combination of the cell of origin and particular mutations. Newest Articles The ASCO Post With increasing cure rates comes increasing concern about their long-term health. If considered a new primary tumor, local regional therapy will be followed by systemic therapy as deemed necessary. In the study, with a median 6.3 years of follow-up, 274 cases of contralateral breast cancer … Each year, a new primary cancer develops in about 14 of every 1000 women with breast cancer, and half of these cancers occur in the contralateral breast. Opposite Breast Risk The Internet’s first and only contralateral breast cancer calculator that provides your odds of getting breast cancer in your other breast based on your prior cancer's estrogen receptor. Importance: The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. The reported incidence is between 1.9% and 6% in different publications [ 1 , 2 ] . The invasive status of the contralateral tumour diagnosis and tumour morphology was collected. Determination of the origin of the breast cancer cells and regulation of ER expression are central to understanding CBC. Studies with microarray analysis have provided insight into the understanding that distinct molecular profiles exist that can be useful in classifying tumors and predicting outcome.17,22 A recent report suggests that genetic analysis using DNA from paraffin-embedded tissue in combination with statistical tools can more accurately classify dual-site cancers.23 In the future, molecular profiling or other laboratory based studies in combination with histopathologic analysis will delineate the true origin of CBCs as either new primary cancers or recurrences. The present communication concerns a study to evaluate the role of various clinico-pathological factors on the occurrence of contralateral breast cancer. The actuarial risk of contralateral breast cancer was 29.5% at 10 years. 23, no. ASCO Author Services Contralateral breast cancer is the most common second cancer in women with primary breast cancer. Lancet 351:: van't Veer LJ, Dai H, van de Vijver MJ, et al: Gene expression profiling predicts clinical outcome of breast cancer. It is known that a false-negative ER result can be obtained with this assay because of receptor occupancy with tamoxifen.10 Because the median interval to CBC diagnosis was 3 years, it is probable that many of these patients were being treated with tamoxifen. These critical investigations will be essential for the understanding of the etiology of breast cancer. Contralateral breast cancer uncommon among women with ductal carcinoma in situ Fewer than 6% of women with ductal carcinoma in situ developed contralateral breast cancer within 10 years, … 1 The study used tissues and clinical details from patients with contralateral breast cancer (CBC), and for the first time, next-generation sequencing (NGS) 2 conclusively showed that a tumor in the contralateral breast … J Natl Cancer Inst 96:: McCaskill-Stevens W: Hormone receptor concordance and predictors of contralateral breast cancer in Surveillance, Epidemiology, and End Results (SEER) population-based registries, Frontiers in Cancer Prevention Research , Seattle, WA, October. Archive Gene expression profiling has suggested ER-positive and ER-negative tumors are distinct tumor types.17 Different molecular phenotypes have been reported for the ER-positive/luminal-like and ER-negative basal tumors.17 Recently, a model has been developed proposing that ER-positive and ER-negative tumors arise from separate subpopulations of stem and progenitor cells.18 On the basis of this model, three different subtypes of breast cancer could occur based on the cell of origin. J Clin Oncol 14:: Early Breast Cancer Trialists' Collaborative Group: Tamoxifen for early breast cancer: An overview of the randomised trials. Radiation Epidemiology Branch (REB) investigators and collaborators from the Kaiser health maintenance organization have developed a retrospective cohort of about 7,000 breast cancer patients diagnosed since 1991. Lancet 1:: Perou CM, Sorlie T, Eisen MB, et al: Molecular portraits of human breast tumours. Since its initial proposal, the multistep process has been well accepted as the route by which tumors arise.13 Breast cancers likely emerge from inherited or acquired mutations in stem or early progenitor cells.14 Mammary stem cells have only recently been isolated by identifying tumorigenic cells based on cell-surface marker expression.15 These stem cells represent important targets for mutations because they are slow-dividing, long-lived cells that may be exposed to various damaging agents over time, leading to a series of alterations that ultimately leads to carcinoma. Harvey EB, Brinton LA: Second cancer following cancer of the breast in Connecticut, 1935-82. JCO Clinical Cancer Informatics Breast cancer survivors constitute about 25% of the growing population of cancer survivors in the US. Br J Cancer 8:: Reya T, Morrison SJ, Clarke MF, et al: Stem cells, cancer, and cancer stem cells. PURPOSE: As local therapies improve, contralateral breast cancer (CBC) risk for women with ductal carcinoma in situ (DCIS) may exceed the risk of a second ipsilateral breast cancer. A woman with unilateral breast cancer has an increased risk of having cancer in the contralateral breast. In addition, the development contralateral breast cancer is associated with a greater risk of dying from breast cancer … Cancer 17:: Lewison EF, Neto AS: Bilateral breast cancer at the Johns Hopkins Hospital: A discussion of the dilemma of contralateral breast cancer. Radiation Epidemiology Branch - Research Areas, Discovering the causes of cancer and the means of prevention, Tumor Profiling in Relation to Cancer Etiology, Risk Assessment Macros and Software Programs, U.S. Department of Health and Human Services. Nature 415:: Brinkmann D, Ryan A, Ayhan A, et al: A molecular genetic and statistical approach for the diagnosis of dual-site cancers. ER status was determined using a ligand-binding assay in the current study. Nature 406:: Dontu G, El-Ashry D, Wicha MS: Breast cancer, stem/progenitor cells and the estrogen receptor. At the current time, we would not recommend tamoxifen for ER-negative primary tumors given the insufficient data supporting any benefit in such a situation. JCO Precision Oncology, ASCO Educational Book The authors indicated no potential conflicts of interest. Purpose The Women’s Environmental Cancer and Radiation Epidemiology (WECARE) study demonstrated the importance of breast cancer family history on contralateral breast cancer (CBC) … There is no apparent increase in risk of developing a contralateral breast cancer between invasive ductal or invasive lobular carcinoma. Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Department of Health and Human Services, Bethesda, MD, Professional English and Academic Editing Support, Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update, Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline, Prognostic Index for Acute- and Lymphoma-Type Adult T-Cell Leukemia/Lymphoma, Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (monarchE), Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer, Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology Clinical Practice Guideline Update, Patient-Clinician Communication: American Society of Clinical Oncology Consensus Guideline, Updating the American Society of Clinical Oncology Value Framework: Revisions and Reflections in Response to Comments Received, American Society of Clinical Oncology Statement: A Conceptual Framework to Assess the Value of Cancer Treatment Options, Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial. Cancer 28:: Arpino G, Weiss HL, Clark GM, et al: Hormone receptor status of a contralateral breast cancer is independent of the receptor status of the first primary in patients not receiving adjuvant tamoxifen. Fisher B, Costantino JP, Wickerham DL, et al: Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. Editorial Roster ASCO Career Center One of the fundamental goals for assessment of ER in any breast tumor is treatment selection. However, is it really important to make the distinction of a new primary or metastases? Differences among study populations may have led to disparate results from previous studies. Abstract An increasing number of women is surviving breast cancer and due to that at risk of developing an isolated ipsilateral breast tumor recurrence (IBTR) or a contralateral breast cancer (CBC). ASCO Connection DOI: 10.1200/JCO.2005.01.910 Journal of Clinical Oncology WECARE: The Women’s Environment, Cancer And Radiation Epidemiology Study One in eight women will develop a primary breast cancer during her lifetime and 5-10% of these women will subsequently develop a second primary cancer in the contralateral breast. Breast Cancer Res Treat 26:: Harvey JM, Clark GM, Osborne CK, et al: Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. Permissions, Authors If applied to CBC, this theory could support the notion that CBC may represent a metastatic lesion that has developed in the primed contralateral breast where the necessary homeostatic factors are present. Cancer.Net, ASCO.org Advertisers, Journal of Clinical Oncology Chi-square tests were undertaken to examine the differences in contralateral rates for both registries and univariate analysis to ascertain which predictors affected contralateral breast cancer … Nature 414:: Al-Hajj M, Wicha MS, Benito-Hernandez A, et al: Prospective identification of tumorigenic breast cancer cells. Published online (July 20, 2005) CBCs are often more difficult to treat than the … Meeting Abstracts, About JCO Oncology Practice DOI: 10.1200/JCO.2005.01.910 Journal of Clinical Oncology - It has long been debated whether ER-positive and ER-negative tumors either originate from distinctly different cells or represent a continuum. The new cancer can occur in the opposite breast, or in the same breast for women who were treated with breast … This is a provocative question, which cannot be answered by our current limited knowledge of the biology of these contralateral cancers. Contralateral breast cancer is of etiological interest because there may be shared risk factors between the first and second primaries (e.g., a family history of breast cancer), whereas other … Although rare, it is very clinically relevant, as lymph node metastasis is the most important prognostic factor in breast cancer. Contralateral breast cancer (CBC) is becoming an important public health issue because of the increased incidence of primary breast cancer and improved survival. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer … For more information, contact Amy Berrington de González. CancerLinQ Chi-square tests were undertaken to examine the differences in contralateral rates for both registries and univariate … published online before print Tamoxifen improves survival of women with ER-positive breast cancers but does not improve survival of women with ER-negative tumors.21 Also, the risk of CBC is reduced by 45% after 5 years of tamoxifen therapy,21 and incidence of invasive cancer decreased by 49% with primary tamoxifen chemoprevention.9 A majority of the patients in the current report, in the absence of adjuvant therapy, were diagnosed with an ER-positive CBC regardless of the hormone receptor status of the PBC. For the cancer to metastasize, certain features must be present. At this time, it is still unclear how initial tumor ER expression develops and later correlates with a subsequent CBC. Enter words / phrases / DOI / ISBN / authors / keywords / etc. The authors conclude that women with advanced-stage primary breast cancer have a heightened risk of developing contralateral breast cancer. JCO Global Oncology Contralateral primary breast cancer diagnosis, Other second cancer diagnosis, Exited the Kaiser Permanente plan, Death, Last tumor-registry follow-up, or; End of study date in 2011. We aimed to … This is in contrast to other studies showing that the receptor status between the PBC and the CBC is concordant.7,8 In the current study, 193 pairs of PBC and CBC with estrogen receptor (ER) and/or progesterone receptor (PgR) assays performed in central laboratories were identified. Objectives: To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer … September 21, 2016. ASCO Daily News We aimed to evaluate whether postdiagnosis use of COX-2 selective or other nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of contralateral breast cancer (CBC) among Danish breast cancer … Proc Natl Acad Sci U S A 100:: Paget S: The distribution of secondary growths in cancer of the breast. J Natl Cancer Inst 90:: Encarnacion CA, Ciocca DR, McGuire WL, et al: Measurement of steroid hormone receptors in breast cancer patients on tamoxifen. Contralateral Breast Cancer. The answer to this question has both prognostic and predictive importance. Institutions A lower frequency of ER-positivity is seen as tumors increase in size, implying that ER expression is blocked as tumors grow.11,19 Furthermore, a certain percentage of patients with ER-positive tumors develop ER-negative metastases.20 Thus, the true origins of ER-positive and ER-negative tumors have yet to be elucidated. Patients' … In the current study, the median age of diagnosis of the PBC was 62 years, with a CBC developing at a median interval of 3 years. Tumor tissue samples from both the first and second breast cancers and mammography films have also been collected. Cookies, Authors' Disclosures of Potential Conflicts of Interest. 21 We sought to … September 21, 2016. By linking electronic treatment files and the Kaiser cancer registries for information on subsequent cancers, researchers have developed a rich resource for studying the late effects of breast cancer treatments. Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. Reviewers Diagnostic criteria for CBC have been described,4,5 but it may be difficult to differentiate between metastasis and a new primary because of a lack of universally accepted criteria. 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