Correlate effects of local therapy for the primary tumor in metastatic breast cancer at diagnosis with molecular subtypes.

e11502 Background: Few studies demonstrated that surgical resection of the primary tumor in patients with metastatic breast cancer at diagnosis is associated with significant improvement of survival. The aim of this study is to evaluate the correlation impact of local surgery in metastatic breast cancer at diagnosis with molecular subtypes. Methods: A retrospective study was conducted from 2007 to 2011 in our institution, of all stage IV breast cancer patients; who undergo breast surgery. Clinical , tumor characteristics, molecular subtypes, prognostic factors, therapeutic results data were analyzed. Results: We selected 59 cases. The mean age was 36 years (range: 22-44). 55 % women presented with locally advanced breast cancer with 13% T4 d . All patients underwent mastectomy except 4 who underwent conservative surgery .41 patients had axillary lymph node dissection. 63% were luminal A, 17% were luminal B, 7% were Her2-positive and 13% were basal-like . All patients received anthracycline based regimen and only 33% received taxanes. Loco regional radiotherapy (RT) was given to 6 women. Average follow-up was 13 months: - 20 patients represented partial response : 15 patients in luminal A , 3 patients in luminal B ,1 patients in basal-like and 1 patient in HER2-positive. - 11 patients (19%) were stable : 9 patients in luminal A and 2 patient in luminal B . -24 patients represented a progressive disease including 11 patients presented locoregional recurrence : 75 % in HER-positive, 40 % in basal-like, 50% in luminal B and 30% in luminal A (p=0.4). - 4 patients died in basal-like. The median local recurrence-free survival was 19 months and the median progression-free survival was 20 months. The local relapse is less observed in patients who: have a small tumor size (p = 0.003), had axillary lymph node dissection (p = 0.02) and loco regional radiotherapy (p = 0.03). The metastatic progression is less observed in patients with small tumor size (p = 0.01). Conclusions: Local Therapy of the primary tumor improves local control of disease, particularly in women with Small tumors. However, no significant correlation between impact of locale therapy and Molecular Subtypes was observed.

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Luminal Subtypes Predict Improved Survival Following Central Nervous System Metastasis in Patients With Surgically Managed Metastatic Breast Carcinoma

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2012-0541-oa ◽

2014 ◽

Vol 138 (2) ◽

pp. 175-181 ◽

Cited By ~ 7

Author(s):

Andrea L. Wiens ◽

Sarah E. Martin ◽

Elizabeth C. Bertsch ◽

Gail H. Vance ◽

Ryan A. Stohler ◽

...

Keyword(s):

Breast Cancer ◽

Central Nervous System ◽

Nervous System ◽

Estrogen Receptor ◽

Metastatic Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Metastatic Breast ◽

Luminal A ◽

Luminal B

Context.—Metastatic breast cancer to the central nervous system (CNS) is second only to lung cancer metastasis to the CNS in frequency. Patients with triple-negative primary breast cancer and those with human epidermal growth factor receptor 2 (HER2)–positive primary breast cancer are at an increased risk for metastasis. Very little is known about predictive or prognostic variables once patients develop CNS metastases. Currently, therapeutic options are limited, with surgery generally offered primarily to those with solitary lesions. Context.—To determine the influence of molecular subtypes of metastatic breast cancer on survival from the time of CNS metastasis and to aid in the prognostic stratification of these patients. Design.—We identified 59 cases of metastatic breast cancer to the CNS and analyzed them for various demographic and clinicopathologic parameters. Tumors were categorized into molecular subtypes using immunohistochemical methods: luminal A [estrogen receptor (ER)+/Ki67low], luminal B (ER+/Ki67 high), intrinsic HER2 (ER−/HER2+), and triple-negative. Survival after CNS metastasis for each group was plotted using a Kaplan-Meier curve, and multivariate analysis was performed. Results.—Patients with metastases from luminal tumors had a statistically significant survival advantage when compared with those of the triple-negative phenotype. Importantly, survival among patients with luminal A and luminal B tumors was not significantly different. Similarly, patient's age, histologic grade, and number of lesions did not contribute to determining outcomes. Conclusions.—Estrogen receptor positivity (ie, luminal phenotype) of tumors appears to determine outcomes after development of metastases. In contrast, proliferation rate had little or no effect on the long-term survival. Understanding the biology of metastases can help stratify patients into prognostically meaningful categories and tailor treatment regimens for individual patients.

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Inflammatory Breast Cancer: Clinical Characteristics and Influence of Molecular Subtypes on Treatment Response

Tumori Journal ◽

10.1177/03008916211012341 ◽

2021 ◽

Vol 107 (1_suppl) ◽

pp. 12-12

Author(s):

D Aissaoui ◽

M Bohli ◽

R Ben Amor ◽

J Yahyaoui ◽

A Hamdoun ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Response ◽

Inflammatory Breast Cancer ◽

Hormone Receptor ◽

Triple Negative ◽

Molecular Subtypes ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Significant Difference

Introduction: Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer with poor prognosis. The prevalence is different from a country to another. In Tunisia, it is about 5 to 7% of breast cancer. The aim of this study is to describe the epidemiological and histopathological features of patients with inflammatory breast cancer and to evaluate the treatment response according to the molecular subtypes. Methods: This retrospective review identified 31 patients with no metastatic IBC treated in our radiotherapy department between December 2019 and November 2020. IBC was confirmed using the clinical criteria. Baseline clinic-pathological and treatment information was retrieved from medical records. Statistical analysis was performed with IBM SPSS V.20. Results: Median age was 51.3 years [27-68]. 48% of tumors were grade 3. The average tumor size was 36mm [10-90]. The histological type was ductal carcinoma in 97%. Vascular invasion was noted in 24 patients (77%). Thirty patients were classified as stage IIIB and one patient was IIIC. 74% were hormone receptor positive and 45% were HER2 positive. Luminal B was the predominant subtype (52%) followed by Her2 positive (32%), Luminal A (23%), and triple negative (3%) All patients had chemotherapy: neoadjuvant for 26 patients (84%) and adjuvant for 5 patients (16%). Nine patients (29%) had tumor pathological complete response (pCR). Partial response was observed in 18 patients (58%). Lymph node pCR was noted in 16% of cases (n=5). Endocrine therapy and trastuzumab were given to 76% and 45% of patients, respectively. The influence of the molecular subtype was not statistically significant on the response to neoadjuvant treatment. The highest rate of pCR were 43% for Her2positive, then 27%, 21% and 9% for Luminal B, Luminal A and Triple negative, respectively (p=0.2). Conclusion: Our study showed a high percentage of hormone receptor and Her2+ (74% and 45% respectively) in IBC. Luminal B was the most frequent subtype. Anthracycline-based chemotherapy and trastuzumab improved the pCR rate: 44% for Her2positive. Triple negative showed poorer pCR than other breast cancer subtype without a significant difference. A larger study is warranted to confirm our findings.

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Trends in breast cancer mortality according to molecular subtypes: A population-based study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.572 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 572-572

Author(s):

Yunan Han ◽

Shuai Xu ◽

Graham A. Colditz ◽

Adetunji T. Toriola

Keyword(s):

Breast Cancer ◽

Cancer Mortality ◽

Triple Negative ◽

Molecular Subtypes ◽

Breast Cancer Mortality ◽

Treatment Strategies ◽

Luminal A ◽

Her2 Positive ◽

Mortality Trends ◽

Luminal B

572 Background: Breast cancer is the second leading cause of cancer death in U.S. women. On the molecular level, breast cancer is a heterogeneous disease. Heterogeneous expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) are etiologically and clinically meaningful, as they map to distinct risk factors and different treatment strategies. Although breast cancer mortality has been declining since 1990, little is known about mortality trends according to molecular subtypes at the population level. Methods: We examined the incidence-based mortality rates and trends among women who were diagnosed with invasive breast cancer from 2010 through 2017 using the Surveillance, Epidemiology, and End Results (SEER) database. We defined incidence-based mortality using a moving 5-year calendar period starting in 2014. We further assessed mortality according to breast cancer molecular subtypes: luminal A (ER and/or PR positive, HER2 negative), luminal B (ER and/or PR positive, HER2 positive), HER2-enriched (HER2 over-expressed or amplified, ER and PR negative) and triple-negative (ER and PR negative, HER2 negative) tumors. We calculated annual percent changes (APC) in incidence-based mortality using joinpoint regression models. Results: Overall, incidence-based mortality for breast cancer significantly decreased by 1.5% annually from 2014 through 2017 (APC, -1.5%; 95% coefficient interval [CI], -2.3% to -0.7%; p<0.001). Incidence-based mortality decreased annually by 2.0% for luminal A breast cancer (APC, -2.0%; 95% CI, -3.7% to -0.3%; p<0.001), 2.1% for luminal B breast cancer (APC, -2.1%; 95% CI, -5.4% to 1.4%; p=0.1), 1.1% for triple-negative breast cancer (TNBC) (APC, -1.1%; 95% CI, -2.1% to -0.0%; p<0.001). However, incidence-based mortality for HER2-enriched breast cancer increased 2.3% annually during the study period (APC, 2.3%; 95% CI, -2.4% to 7.2%; p=0.2). Conclusions: Between 2014 and 2017, incidence-based mortality for luminal A, luminal B, and TNBC decreased among U.S. women, with a larger decrease observed for luminal tumors. However, incidence-based mortality for HER2-enriched breast cancer increased. The favorable incidence-based mortality trends for luminal tumors and TNBC are likely due to the continuing improvement in treatments and early detection. The increasing trend of incidence-based mortality for HER2-enriched breast cancer constitutes a priority for cancer control activities and further research.

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Breast cancer in Angola, molecular subtypes: The first preliminary study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13075 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13075-e13075

Author(s):

Lúcio Lara Santos ◽

Fernando Miguel ◽

Lygia Vieira Lopes ◽

Julio Oliveira ◽

Eduardo Ferreira ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Locally Advanced ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Therapeutic Decisions ◽

Ihc Markers

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.

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Undetectable Tumor Cell-Free DNA in a Patient With Metastatic Breast Cancer With Complete Response and Long-Term Remission

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2019.7381 ◽

2020 ◽

Vol 18 (4) ◽

pp. 375-379

Author(s):

Natasha Hunter ◽

Sarah Croessmann ◽

Karen Cravero ◽

Daniel Shinn ◽

Paula J. Hurley ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Primary Tumor ◽

Large Scale ◽

Residual Disease ◽

Metastatic Breast ◽

Liquid Biopsies ◽

Her2 Positive ◽

Cell Free Dna ◽

Free Dna

The ability to serially monitor tumor-derived cell-free DNA (cfDNA) brings with it the potential to measure response to anticancer therapies and detect minimal residual disease (MRD). This report describes a patient with HER2-positive metastatic breast cancer with an exceptional response to trastuzumab and nab-paclitaxel who remains in complete remission several years after cessation of therapy. Next-generation sequencing of the patient’s primary tumor tissue showed several mutations, including an oncogenic hotspot PIK3CA mutation. A sample of cfDNA was collected 6 years after her last therapy and then analyzed for mutant PIK3CA using digital PCR. No detectable mutations associated with the primary tumor were found despite assaying >10,000 genome equivalents, suggesting that the patient had achieved a molecular remission. Results of this case study suggest that serial monitoring of MRD using liquid biopsies could provide a useful method for individualizing treatment plans for patients with metastatic disease with extreme responses to therapy. However, large-scale clinical studies are needed to validate and implement these techniques for patient care.

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First results of a prospective registry in unresectable locally advanced or metastatic breast cancer patients: GEICAM/2014-03 (RegistEM).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.1077 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 1077-1077

Author(s):

Carlos Jara ◽

Isabel Alvarez ◽

Mireia Margeli Vila ◽

Cesar Augusto Rodriguez ◽

Purificacion Martinez ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Advanced Disease ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Metastatic Breast ◽

Primary Breast Tumor ◽

Luminal A ◽

Luminal B ◽

First Diagnosis

1077 Background: In Spain there is limited prospective data for unresectable locally advanced breast cancer (ULABC) or metastatic breast cancer (MBC) patients (pts) treated as per clinical practice. RegistEM study will provide epidemiological, pathological and clinical data, including treatments given for different disease stages. Understanding the real distribution of the different BC subtypes is the primary objective. Methods: This is a non-interventional cohort study enrolling approximately 1,400 pts with advanced disease diagnosed from January 2016 to December 2018, either after recurrence or as first diagnosis, in 38 Spanish sites. Biological samples (primary tumor, metastatic lesions, blood) are currently being collected. In this first analysis, we include 489 pts who met study criteria before October 31, 2017. All data are described in two subgroups: on the most recent tumor lesion or on the primary breast tumor. Results: At first diagnosis, 67.9%, 31.5% and 0.6% of pts had early BC (EBC), MBC and ULABC, respectively. In the total analysis population, median age at diagnosis of advanced disease was 59.6 years, most of pts were white (98.2%), female (99.4%) and postmenopausal (70%). Family history of BC and ovarian cancer was reported in 5.7% pts. In ~390 pts BC clinical subtypes distribution was luminal B(HER2-)-like (~55%), luminal B(HER2+)-like (~16%), luminal A-like or triple negative (TN) (~10% each) and HER2 enriched-like (~8%). Median time to recurrence (years) in EBC pts was: luminal A-like 5.8, luminal B(HER2-)-like 5.1, luminal B(HER2+)-like 3.9, HER2 enriched-like 2.7 and TN 1.7. Bone (59%), visceral (58%) and lymph node (27%) lesions were the most frequent metastatic locations. The two most frequent therapies in first line consisted in: endocrine therapy (ET) (47%) and ET+biological therapy (BT) (29%) for luminal A-like; ET (32%) and ET+BT (32%) for luminal B(HER2-)-like; chemotherapy (CT)+ET+BT (43%) and CT+BT (24%) for luminal B(HER2+)-like; CT+BT (68%) and CT (16%) for HER2 enriched-like; CT (59%) and CT+BT (34%) for TN. Conclusions: These first data confirm that luminal B (HER2-)-like subtype is the most predominant in MBC.

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Predicting the Incidence and Prognosis of Bone Metastatic Breast Cancer: A SEER-Based Observational Study

BioMed Research International ◽

10.1155/2020/1068202 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Dongning Shi ◽

Junwen Bai ◽

Yibo Chen ◽

Xia Wang ◽

Yafeng Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Large Population ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Luminal A ◽

Luminal B ◽

The Impact

Background. To determinate the association relationship of breast cancer bone metastasis and cancer characteristics and molecular subtype. Furthermore, to evaluate the impact of molecular subtype on prevalence and prognosis of bone metastasis from the breast cancer base on a large population real-word program, the Surveillance, Epidemiology, and End Results (SEER) database. Methods. We collected and analyzed the data obtained from SEER, which showed molecular subtype information for each patient. The prevalence and outcome of bone metastasis in breast cancer were estimated as per the different molecular subtypes. Results. Occurrence of bone metastasis in conformity with four different molecular subtypes in all 42684 breast cancer patients was 6.2, 9.4, 7.9, and 6.4%, respectively. The most unfavorable subtype was the triple-negative breast cancer (TNBC), followed by the luminal A, luminal B, and HER2 subtypes (hazard ratio [HR] of luminal A compared with TNBC, 0.533, 95% confidence interval, 0.444–0.641; HR of luminal B, 0.482, 95% CI 0.419–0.555; HR of HER2 subtype, 0.542, 95% CI 0.484–0.608). Brain metastasis impacts overall survival (OS) ( p < 0.001 ) fundamentally, and visceral metastases also significantly decreased OS ( p < 0.001 ). Conclusion. Bone metastasis patients present a more favorable oncological survival consequence than other metastases, and the TNBC subtype with bone metastasis showed the poorest tumor outcome compared with the other three molecular subtypes.

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Real-world, single-centre prospective data of age at breast cancer onset: focus on survival and reproductive history

BMJ Open ◽

10.1136/bmjopen-2020-041706 ◽

2021 ◽

Vol 11 (1) ◽

pp. e041706

Author(s):

Peeter Karihtala ◽

Anniina Jääskeläinen ◽

Nelli Roininen ◽

Arja Jukkola

Keyword(s):

Breast Cancer ◽

Cancer Diagnosis ◽

Survival Rates ◽

Age Groups ◽

Metastatic Breast ◽

Breast Cancer Diagnosis ◽

University Hospital ◽

Luminal A ◽

Her2 Positive ◽

Luminal B

ObjectivesBeing either young or old at the time of breast cancer diagnosis has been suggested as an indicator of a poor prognosis. We studied the effect of age at breast cancer onset in relation to survival, focusing in particular on biological subtypes and reproductive anamnesis.Design, setting and participantsPatients with early breast cancer (n=594) treated in a Finnish University Hospital during 2003–2013 were prospectively collected and followed in median 102 months.ResultsPatients with luminal A-like breast cancer were older than the patients with luminal B-like (HER2-positive) (p=0.045) or patients with the HER2-positive (non-luminal) subtype (p=0.029). Patients ≥70 years received substantially less adjuvant chemotherapy (p=1.5×10−9) and radiotherapy (p=5.9×10−7) than younger women. Nevertheless, the estimated 10-year breast cancer-specific rates of survival were 84.2%, 92.9% and 87.0% in age groups <41 years, 41–69 years and ≥70 years, respectively, with no statistical difference (p=0.115). Survival rates were also comparable between the three age groups when assessed separately in different biological subtypes, and for patients with metastatic breast cancer there was similarly no difference between the age groups. Later menarche (p=5.7×10−8) and high parity (p=0.000078) correlated with increased age at breast cancer diagnosis, but, according to the patients’ oestrogen receptor (ER) status, only among ER-positive patients.ConclusionsDespite the suggested undertreatment of older patients, we report excellent long-term outcomes in all age groups in this prospective cohort. Later endogenous endocrine exposure may cause delay in breast cancer onset, but the exact biology behind this phenomenon is so far unclear.

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Role of Tumor Subtypes in Response to Neoadjuvant Chemotherapy in Non-metastatic Breast Cancer

Archives of Iranian Medicine ◽

10.34172/aim.2021.132 ◽

2021 ◽

Vol 24 (12) ◽

pp. 881-886

Author(s):

Negar Mashoori ◽

Ramesh Omranipour ◽

Abdolali Assarian

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Pathologic Complete Response ◽

Metastatic Breast ◽

Tumor Grade ◽

Her2 Status ◽

Luminal A ◽

Luminal B ◽

Female Patients

Background: Neoadjuvant chemotherapy (NAC) is an integral part of breast cancer treatment. Determination of the factors that can distinguish patients who will have best response to NAC is invaluable. In this study, we aimed to elucidate the factors influencing patient response to NAC. Methods: We retrospectively collected data of female patients with non-metastatic breast cancer that had received NAC followed by surgery, admitted to Imam Khomeini hospital between 2015–2019. We investigated the association between various tumor and patients’ characteristics with pathologic complete response (PCR). Results: Overall data of 205 female patients were collected. PCR was observed in 27.6% of cases. PCR rate in luminal A, luminal B, HER2 enriched, and TNB tumors was reported in 11.1%, 30.2%, 35.7%, and 36.4% of patients respectively (P=0.27). In patients with luminal B tumors, PCR was more prevalent in patients with positive HER2 only (P=0.006). In our study factors which was significantly associated with PCR were: tumor grade, progesterone receptor (PR) status, and HER2 status. In the multiple regression model, positive PR in the tumor lowered the odds of pathologic response 3.6 times (P=0.004). Conclusion: In our study, tumor grade, PR status, and HER2 status was associated with response to NAC. PCR was more prevalent in non-luminal tumors; however, PCR rate in luminal B patients-especially those with HER2 positive status- was slightly less than non-luminals.

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