Variability in reexcision following breast conservation surgery.
McCahill LE, Single RM, Aiello Bowles EJ, Feigelson HS, James TA, Barney T, Engel JM, Onitilo AA.
Richard J. Lacks Cancer Center, Van Andel Research Institute, and Department of Surgery, Michigan State University, Grand Rapids, MI 49503, USA. mccahill@trinity-health.org
Comment in JAMA. 2012 Feb 1;307(5):509-10.
CONTEXT: Health care reform calls for increasing physician accountability and transparency of outcomes. Partial mastectomy is the most commonly performed procedure for invasive breast cancer and often requires reexcision. Variability in reexcision might be reflective of the quality of care. OBJECTIVE: To assess hospital and surgeon-specific variation in reexcision rates following partial mastectomy. DESIGN, SETTING, AND PATIENTS: An observational study of breast surgery performed between 2003 and 2008 intended to evaluate variability in breast cancer surgical care outcomes and evaluate potential quality measures of breast cancer surgery. Women with invasive breast cancer undergoing partial mastectomy from 4 institutions were studied (1 university hospital [University of Vermont] and 3 large health plans [Kaiser Permanente Colorado, Group Health, and Marshfield Clinic]). Data were obtained from electronic medical records and chart abstraction of surgical, pathology, radiology, and outpatient records, including detailed surgical margin status. Logistic regression including surgeon-level random effects was used to identify predictors of reexcision. MAIN OUTCOME MEASURE: Incidence of reexcision. RESULTS: A total of 2206 women with 2220 invasive breast cancers underwent partial mastectomy and 509 patients (22.9%; 95% CI, 21.2%-24.7%) underwent reexcision (454 patients [89.2%; 95% CI, 86.5%-91.9%] had 1 reexcision, 48 [9.4%; 95% CI, 6.9%-12.0%] had 2 reexcisions, and 7 [1.4%; 95% CI, 0.4%-2.4%] had 3 reexcisions). Among all patients undergoing initial partial mastectomy, total mastectomy was performed in 190 patients (8.5%; 95% CI, 7.2%-9.5%). Reexcision rates for margin status following initial surgery were 85.9% (95% CI, 82.0%-89.8%) for initial positive margins, 47.9% (95% CI, 42.0%-53.9%) for less than 1.0 mm margins, 20.2% (95% CI, 15.3%-25.0%) for 1.0 to 1.9 mm margins, and 6.3% (95% CI, 3.2%-9.3%) for 2.0 to 2.9 mm margins. For patients with negative margins, reexcision rates varied widely among surgeons (range, 0%-70%; P = .003) and institutions (range, 1.7%-20.9%; P < .001). Reexcision rates were not associated with surgeon procedure volume after adjusting for case mix (P = .92). CONCLUSION: Substantial surgeon and institutional variation were observed in reexcision following partial mastectomy in women with invasive breast cancer.
PMID: 22298678 [PubMed - in process]
2-18-12 entry
Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy http://www.ncbi.nlm.nih.gov/pubmed/21900114 The 5-year cumulative incidence of LR was 0.8% (95% CI, 0.4% to 1.8%)
for luminal A; 2.3% (95% CI, 0.8% to 5.9%) for luminal B; 1.1% (95% CI,
0.2% 7.4%) for luminal HER2; 10.8% (95% CI, 4.6% to 24.4%) for HER2; and
6.7% (95% CI, 3.6% to 12.2%) for triple negative.
2-28-12 entry
Fewer women need repeat breast cancer surgeries with new service at University of Michigan
DEAD box 1 (DDX1) expression predicts for local control and overall survival in early stage, node-negative breast cancer http://onlinelibrary.wiley.com/doi/10.1002/cncr.26352/abstract DDX1 is low in TNBC and DDX1 expression is correlated with good outcome.
Another view of DDX1 is that it is a marker of TNBC vs other forms of BC. All of the TNBC markers are going to be associated with worse prognosis because TNBC itself has a worse prognosis than other BCs. But each marker is one step closer to drugable targets and specific therapies for TNBC.
Re: latest controversies re: lumpectomies you posted above.
first of all, thank you for posting it but I have a question-
How many of the cases were TNBC? If we don’t know how many were I am not certain that this information is pertinent for our community.
I don’t have the time to look at the data..do you know if the large number of cases were broken down as to subtypes of breast cancer or for this study all invasive breast cancer is considered one cancer?
thanks if you can illuminate.
warmly,
Steve
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates
No breakdown at all into different types of BC. It's a look at how often re-excision has to be done. The point of the paper is to highlight the lack of an industry standard for determining when lumpectomies should be done (anywhere from 1cm to 4cm tumor size), and how much of a negative margin there should be. Obviously these decisions have bearing on recurrence rates, irrespective of BC types.
I don’t mean to be a pain...My point is that I feel TNBC is a separate beast with six heads....Ideally I would like to see research done on all the TNBC subtypes but that is years away, I would imagine but in the meantime, whenever I see a study, I want to try to make sure whatever studies mentioned in this thread is pertinent to our community. Studies looking at ‘all’ breast cancer include TNBC but again I don’t know how pertinent this is for us because we are dealing with TNBC, not all breast cancer.
The bottom line question being addressed here I think are the disparities in margins across the country..This doc, from what I understand, wants to have national standards. That is a tough project, in my opinion because different surgeons seem to have different philosophies and they want their independence.
TNBC is particularly troublesome from what I understand because there is often microscopic components so it makes it difficult to know, with any certainty, whether the surgeon had clean margins. And with Invasive Ductal Carcinoma which categorizes most TNBC we have seen lots of recurrences in our TNBC family. So should there be separate guidelines for ‘margins’ for TNBC? and how can that be addressed if the McCahill cohort does not differentiate between various subtypes of breast cancer, especially, for our perspective, TNBC?
warmly,
Steve
Edited by steve - Feb 03 2012 at 10:15pm
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates
Agreed that the biology of TNBC is distinct from other breast cancers with primary tumor size and node status being less predictive of long term outcome in TNBC. So there is an argument that the optimal surgical approach for TNBC might be different from other BCs, and at the very least TNBC should be split out in studies. But where we are today, many surgeons and much of the surgical literature seems to approach all BC generically. Still relevant to TNBC, and if we want to stay on top of surgical issues, we are going to have to look at the broader literature.
Standardization of surgical approach is an important first step. If the surgeons cannot even agree among themselves about what constitutes "clean margins" and the necessity of re-op if there is residual tumor, how are we even going to begin to look at how TNBC should be approached vs. other tumor types?
Dense breasts have been a forum topic and I found these articles that may be of help. In my own case, my 2009 mammogram said I had dense breasts and mammogram quality was poor but otherwise normal. Neither the radiologist or the primary doc (at a major medical center) I was seeing thought to follow up with me about the risk associated with dense breasts.
I wonder how many similar situations are out there.
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates
*Long term effects of chemobrain. LBBC podcast* (posted 2/26/12 LBBC has a podcast form 5/25/11: Long term effects of chembrain uncovered. If one goes to: http://www.lbbc.org/ Put in the search box: chemobrain (not chemo brain)
*chemobrain info from American Cancer Society* (posted 2/26/12) http://www.cancer.org/ using search: type in chemo brain. Choose chemo brain. (not chemobrain)
*chemo brain info from Mayo clinic site* (posted 2/26/12) http://www.mayoclinic.com/ using search: type in chemo brain. Choose chemo brain. (not chemobrain)
*chemo brain info from cancercare* (posted 2/26/12) http://www.cancercare.org/ Click on Help by Diagnosis or topic. Under Topics: Click on chemo brain. Click on pod cast or publication one wants.
* Some books on chemo brain* (posted 2/26/12) Chemo brain How Cancer Therapies Can Affect Your Mind by Ellen Clegg. 2009 Your Brain After Chemo . by Dan Silverman, MD Idelle Davidson. 2009
Gene Reviews. Expert-authored summaries about diagnosis, management and genetic counseling for specific inherited conditions, University of Washington. http://www.ncbi.nlm.nih.gov/books/NBK1116/
*IBC: Identifying factors that impact survival among women with inflammatory breast cancer. Dawood S, Ueno NT, Valero V, Woodward WA, Buchholz TA, Hortobagyi GN, Gonzalez-Angulo AM, Cristofanilli M. (2012 article)
The CLRC has a national, toll-free Telephone Assistance Line (866-THE-CLRC) where callers can receive free and confidential information about relevant laws and resources for their particular situation. Members of the CLRC's Professional Panel of attorneys, insurance agents, and accountants can provide additional assistance. That phone number is 866-843-2572)
1. Int J Radiat Oncol Biol Phys. 2011 Dec 13. [Epub ahead of print]
Oligometastases Treated With Stereotactic Body Radiotherapy: Long-Term Follow-Up of Prospective Study.
Milano MT, Katz AW, Zhang H, Okunieff P.
Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY.
PURPOSE: To analyze the long-term survival and tumor control outcomes after stereotactic body radiotherapy (SBRT) for metastases limited in number and extent. METHODS AND MATERIALS: We prospectively analyzed the long-term overall survival (OS) and cancer control outcomes of 121 patients with five or fewer clinically detectable metastases, from any primary site, metastatic to one to three organ sites, and treated with SBRT. Freedom from widespread distant metastasis (FFDM) was defined as metastatic disease not amenable to local therapy (i.e., resection or SBRT). Prognostic variables were assessed using log-rank and Cox regression analyses. RESULTS: For breast cancer patients, the median follow-up was 4.5 years (7.1 years for 16 of 39 patients alive at the last follow-up visit). The 2-year OS, FFDM, and local control (LC) rate was 74%, 52%, and 87%, respectively. The 6-year OS, FFDM, and LC rate was 47%, 36%, and 87%, respectively. From the multivariate analyses, the variables of bone metastases (p = .057) and one vs. more than one metastasis (p = .055) were associated with a fourfold and threefold reduced hazard of death, respectively. None of the 17 bone lesions from breast cancer recurred after SBRT vs. 10 of 68 lesions from other organs that recurred (p = .095). For patients with nonbreast cancers, the median follow-up was 1.7 years (7.3 years for 7 of 82 patients alive at the last follow-up visit). The 2-year OS, FFDM, and LC rate was 39%, 28%, and 74%, respectively. The 6-year OS, FFDM, and LC rate was 9%, 13%, and 65%, respectively. For nonbreast cancers, a greater SBRT target volume was significantly adverse for OS (p = .012) and lesion LC (p < .0001). Patients whose metastatic lesions, before SBRT, demonstrated radiographic progression after systemic therapy experienced significantly worse OS compared with patients with stable or regressing disease. CONCLUSIONS: Select patients with limited metastases treated with SBRT are long-term survivors. Future research should address the therapeutic benefit of SBRT for these patients.
See earlier post on studies looking at Avastin in TNBC.
Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer http://www.springerlink.com/content/4x84586uvp476v01/ (small prospective study from Spain. Treatment: randomize to 4 cycles of doxorubicin or docetaxel followed by surgery to determine pCR and the cross-over to the other arm for chemo).
Taxanes and anthracyclines improve the outcome of early breast cancer, although the benefit is limited to a small proportion of patients and are toxic. We prospectively looked for predictors of response to these drugs. Experimental design: Four cycles of doxorubicin (75 mg/m²) or docetaxel (100 mg/m²) were compared as presurgical chemotherapy for breast cancer. Biomarkers were determined by immunohistochemistry and fluorescent in situ hybridization using prechemotherapy core biopsies. Tumors were also classified into one of the molecular intrinsic subtypes using an immunohistochemical panel of five biomarkers and genomic profiles. Single genes and intrinsic subtypes were correlated with response to doxorubicin versus docetaxel. Among the 204 evaluable patients, significant predictors of sensitivity in multivariate analysis were low topo2a expression and ER-negative status for doxorubicin and small tumor size and ER-negative status for docetaxel. Predictors of resistance in multivariate analysis were triple-negative status (ER/PgR/HER2 negative by IHC/FISH) for doxorubicin, and high TNM stage for docetaxel. Triple-negative tumors were associated with topo2a overexpression more than the other subtypes. In 94 patients with gene expression profiles, docetaxel was superior to doxorubicin in the basal-like subtype (good pathological response rate - PCR + class I of 56 vs. 0%; P = 0.034); no significant differences were observed in the other subtypes when comparing these two drugs. Low topo2a expression and ER-negative status were predictors of response to doxorubicin, while small tumor size and ER-negative status predicted response to docetaxel. Docetaxel was superior to doxorubicin in triple-negative/basal-like tumors, while no significant differences were seen in the remaining intrinsic subtypes.
2-8-12 entry
Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011 (open access) http://annonc.oxfordjournals.org/content/22/8/1736.short Re-post previous listings
Management options in triple negative breast cancer 2011 Minami, Chung, Chang http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153117/?tool=pubmed Adjuvant Capecitabine, Docetaxel,
Cyclophosphamide, and Epirubicin for Early Breast Cancer: Final Analysis of the
Randomized FinXX Trial
PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer--results at the time of surgery http://www.ncbi.nlm.nih.gov/pubmed/21385882 TNBC group: pCR 44.6% with the dose dense E->T->CMF and 30.4% with EC->T (but not statistically significant)
2-14-12 entry
Weekly paclitaxel in the adjuvant treatment of breast cancer (open access) Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW, Wood WC, Davidson NE http://www.nejm.org/doi/full/10.1056/NEJMoa0707056 doses tested: 175 mg of paclitaxel/m2 x 4 every 3 weeks versus 80 mg of paclitaxel/m2 weekly x12 doses; all patients received AC x4 every 3 weeks CONCLUSIONS: Weekly paclitaxel after standard adjuvant chemotherapy with doxorubicin and cyclophosphamide improves disease-free and overall survival in women with breast cancer. (ClinicalTrials.gov number, NCT00004125 [ClinicalTrials.gov].)
2-15-12 entry
Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study (2010) http://www.ncbi.nlm.nih.gov/pubmed/20697801 The highest pCR rate (57%) was for TNBC patients, < 40 years, grade 3 tumors. Neoadjuvant regimen: TAC x 2 (every 3 weeks) a) if response then proceed with 4 or 6 cycles of TAC; b) no response then randomized to either continue with TAC x 4 or to 4 cycles of vinorelbine and capecitabine) -- all every 3 week regimen.
The paper by Swain et al. is noteworthy for the fact that with the
original concurrent ACT dosing (A 60 mg/m2, C 600 mg/m2 and docetaxel 60
mg/m2 q3 weeks) there were 5 deaths and the protocol had to be amended
to A 50 mg/m2, C 500 mg/m2 and docetaxel 75 mg/m2 q3 weeks while the
sequential ACT continued with A 60 C 600 and docetaxel 100 mg/m2 q3
weeks. G-CSF was also added to the concurrent regimen (there is a 3rd
arm testing A and docetaxel that also got G-CSF). The fact that they had
to back down on the doses for the concurrent protocol might have
contributed to the lower performance of this regimen.
The Swain
paper is on the B-30 trial (National Surgical Adjuvant Breast and Bowel
project NCT00003782) - the ongoing one that is closed that is closer to the DD
schedule is the B-38 trial (NCT00093795).
Update 2-20-12 Patients are node-positive and have early stage operable BC. TNBC was not separated out. Receptor stratification according to ER status only. Interestingly there was no mention of Her2 anywhere in the article.
The B-30 trial and its European counterpart
turtle wrote:
Here's an article and link sent to me by Carey Anders, the
hem/onc I saw at UNC. Until we see the results of the B38 trial, this
is the best info we have for now:
SABCS: Mixed Results for Sequential Versus Concurrent Therapy for Breast
Cancer
By Charles Bankhead, Staff Writer, MedPage Today
Published: December 16, 2008
Reviewed by Robert Jasmer, MD;
Associate Clinical Professor of Medicine, University of California, San
Francisco .
SAN ANTONIO, Dec. 16 -- The debate over the superiority of sequential versus
concurrent adjuvant chemotherapy for breast cancer failed to get a resolution in
two large studies reported here.
Investigators in a North American trial found improved overall survival and
disease-free survival with sequential therapy for patients with early-stage,
node-positive breast cancer.
In contrast, a European-led study with the same types of patients and
sequential and concurrent chemotherapy showed equivalent overall survival and
disease-free survival.
The mixed results, reported at the San Antonio Breast Cancer Symposium, added
data but no closure to an issue that has been examined in several studies on
both sides of the Atlantic.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-30 trial
involved 5,351 patients with node-positive breast cancer. The patients were
randomized to three treatment schedules:
Concurrent docetaxel (Taxotere), doxorubicin (Adriamycin), and
cyclophosphamide (Cytoxan) (TAC) for four cycles
Concurrent doxorubicin and docetaxel for four cycles (AT)
Doxorubicin and cyclophosphamide for four cycles, followed by four cycles of
docetaxel (AC-T)
The trial was designed to answer two questions, said Sandra Swain, M.D., of
Washington (D.C.) Hospital Center: Will concurrent therapy with TAC improve
overall and disease-free survival versus AC-T? Is concurrent therapy with AT at
least as efficacious as TAC and AC-T?
The patients had stage T1-3 on clinical examination and one or more positive
lymph nodes by pathology. Patients with hormone receptor-positive tumors also
received adjuvant tamoxifen.
After a median follow-up of 73 months, the AC-T had a 14% improvement in
overall survival versus TAC (HR 0.86, P=0.086) and a 17% improvement
versus AT (HR 0.83, P=0.034). AT demonstrated noninferiority to TAC,
reflected in a TAC hazard ratio of 0.96.
Sequential AC-T demonstrated a significant advantage for disease-free
survival, reflected in a 17% improvement versus TAC (HR 0.83, P=0.006)
and a 20% improvement versus AT (HR 0.80, P=0.001). AT demonstrated
noninferiority to TAC (HR 0.96).
Analysis of site of first recurrence showed that patients in the TAC arm had
significantly more regional recurrences (35 versus 22 for AT and 16 for AC-T,
P=0.02). The AT regimen was associated with significantly more distance
recurrences (280 versus 257 with TAC and 218 with AC-T, P=0.009).
Subgroup analysis revealed a consistent advantage for sequential therapy,
regardless of age, hormone receptor status, number of involved nodes, primary
tumor size, and menopausal status.
A prespecified secondary objective of the study was to determine whether
amenorrhea (≥6 months without menses) was associated with overall survival or
DFS in premenopausal women.
Dr. Swain reported that amenorrheic women had a 24% improvement in overall
survival (P=0.038) and a 30% improvement in DFS (P=0.00041).
The association existed in all three treatment arms and was unaffected by
patient age or hormone receptor status.
Grade 3-4 toxicity tended to occur more often with sequential therapy, which
was associated with more vomiting, stomatitis, febrile neutropenia, and
infections compared with the other two regimens.
Wolfgang Eiermann, M.D., of the Red Cross Women's Hospital in Munich,
Germany, reported findings from the Breast Cancer International Research Group
005 study of adjuvant chemotherapy in 3,300 HER2-normal women.
All patients had stage T1-3, histologically-proven node-positive breast
cancer. They were all 70 or younger, and all had definitive surgery and axillary
lymph node dissection.
The patients were randomized to six cycles of TAC or to four cycles of AC-T.
Hormone receptor-positive patients also received adjuvant tamoxifen or aromatase
inhibitors for five years.
The primary endpoint was DFS, and secondary endpoints included overall
survival, safety, and quality of life.
After a median follow-up of 65 months, patients randomized to TAC had a DFS
of 78.9% versus 78.6% for the AC-T arm. Overall survival also was similar, 88.9%
with AC-T and 88.1% with TAC. The results did not differ significantly with
respect to number of positive nodes, hormone receptor status, and
triple-negative receptor status.
Sequential therapy was associated with a significantly lower rates of febrile
neutropenia (8.3% versus 17.9%, P<0.0001) and grade 3-4
thrombocytopenia (1.3% versus 2.5%, P=0.01).
In contrast, the AC-T regimen led to higher rates of neuropathy (42.8% versus
27.5%, P<0.0001), nail changes (44.5% versus 22.1%,
P<0.0001), and myalgia (50.9% versus 35.8%, P<0.0001).
The sequential regimen also was associated with higher rates of grade 3-4
arthralgia, neuropathy, fluid retention, hand-foot syndrome, and myalgia.
Updated 2-20-12
Here's the European trial cited in the above article: Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial http://jco.ascopubs.org/content/29/29/3877.abstract Doses tested: TAC (75/50/500 mg/m2 q3 wks) AC (60/600 mg/m2 q3 wks) -> Docetaxel (100 mg/m2 q3 wks) Patients are node positive and have Her2 non amplified operable BC. ** same conclusions applied to the TNBC subset but the 5 year disease free survival is 81% in the ER+ group vs. 68.6% in the TNBC group.
2-19-12 entry A phase II pilot trial incorporating bevacizumab
into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in
patients with lymph node positive breast cancer: a trial coordinated by the
Eastern Cooperative Oncology Group.
Preoperative Systemic Therapy in Breast Cancer (Medscape article from 2010)
http://www.medscape.org/viewarticle/717868 Pay attention to the CALGB 40603 trial for TNBC - just checked clinicaltrials.gov =>study suspended. No reasons given. The GeparQuinto study is closed and the results were published earlier this year in NEJM
2-25-12 entry Clinical correlates of 'BRCAness' in triple-negative breast cancer of patients receiving adjuvant chemotherapy http://www.ncbi.nlm.nih.gov/pubmed/22357256 Smallish study from the Netherlands, 157 TNBC patients of which 65% found to have BRCAness in their tumor profile. BRCAness defined by an assay developed by the same group. Although patient characteristics differ between those with BRCAness vs non-BRCAness, based on this study, there is no difference in 5-year recurrence free survival.
More details:
patients were treated with AC (DD or standard), FEC, TAC or CMF.
Tumors that are BRCA-like had (1) BRCA1 mutations or (2) low levels of BRCA1 messenger RNA or (3) BRCA1 promoter methylation (modification of the DNA sequence that controls transcription of the gene).
Patients with a T3 or T4 tumor had almost 3x the risk for relapse or metastatic disease than patients with a smaller tumor
Patients with BRCA1-like tumors had significantly fewer node+ disease compared to patients with non-BRCA1 like tumor
3-2-12 entry Rapid decrease in delivery of chemotherapy to tumors after anti-VEGF therapy: implications for scheduling of anti-angiogenic drugs http://www.ncbi.nlm.nih.gov/pubmed/22264790 Study in lung cancer but makes the point of the importance of dose scheduling
3-7-12 note I've added a new post on Taxanes, too long to append here. 3-14-12 entry Cancer immunotherapy--revisited http://www.ncbi.nlm.nih.gov/pubmed/21804596 Reason for this entry is the discussion that chemo agents (A, C, T, F, M, platinum) have effects in addition to direct killing of tumor cells. Specifically, effects on the immune system that assist in tumor killing. These are not findings that are readily apparent in in vitro cell line assays, which do not take into account the tumor microenvironment where a lot is happening (interactions between tumor cells and immune cells, vascular endothelium....) Mitosis is not a key target of microtubule agents in patient tumors http://www.nature.com/nrclinonc/journal/v8/n4/abs/nrclinonc.2010.228.html An article that looks at why microtubule targeting agents (e.g. taxanes and epothilones) are effective and why mitosis-specific drugs are not. MTAs are effective because they target not only dividing cells but also non dividing cells by interfering with the microtubule structures and affecting cellular processes such as intracellular trafficking. 3-18-12 entry Recommendations from an International Consensus Conference on the Current Status and Future of Neoadjuvant Systemic Therapy in Primary Breast Cancer http://www.springerlink.com/content/l88k6453022t1528/ (not open access but would recommend that you get the entire article if you are on/had neoadjuvant treatment)
3-26-12 entry Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011 (open access) http://annonc.oxfordjournals.org/content/22/8/1736.full recommend that you take a look - current thinking
While 80-90% of BRCA1-associated tumors are TNBC, no such association is present for BRCA2
MA.5 phase 3 trial: superiority of CMF over CEF in a subset of patients with basal phenotype (small patient size --> not statistically significant)
meta analysis of 5 trials suggests that anthracycline-containing regimens more active than CMF in the TNBC subgroup
Rocca et al. JCO 29:87s, 2011 abstract - E+CMF is more active than CMF (randomized phase) in terms of 5 year disease free survival and overall survival
Lack of convincing evidence supporting a role for EGFR as a driver of BC oncogenesis
striking pCR rates for BRCA1 associated tumors with single agent cisplatin; role for platinums in non BRCA mutated tumors still not clear
good review of current status of PARPi (if you are interested in PARPi, consider obtaining the article from your cancer center): onl veliparib and olaparib are able to inhibit PARP1/2. Iniparib was able to suppress genes involved in telomere function.
although the rationale for the use of PARPi is clear in the cases of BRCA associated tumors, there could still be a benefit for PARPi in non-BRCA associated tumors because many chemo agents cause DNA damage that PARP is needed for repair, hence inhibiting PARPs could act to sensitize chemo agents
BiPar phase 3 study -- although the trial did not meet pre-specificed stats, there is a signal for the Gem/Cisplatin/Iniparib arm, what is not clear is where the signal is coming from.
Two trials relevant to TNBC Paclitaxel With or Without Carboplatin and/or Bevacizumab Followed By
Doxorubicin and Cyclophosphamide in Treating Patients With Breast Cancer
That Can Be Removed by Surgery http://clinicaltrials.gov/ct2/show/NCT00861705?term=NCT00861705&rank=1 Active, 373 sites -- sounds like a whopper of a regimen (T +/- carboplatin or Avastin + DD AC )
There has been a lot of discussion on this forum about the value of different imaging modalities in breast cancer, including metastatic staging at the time of diagnosis. I found this review (open access) that discusses the pros and cons of radiotracer imaging techniques, including SNLBs. One thing I thought interesting is that unless peri-lesional injections (i.e. injections around the tumor) of the tracer/dye are done, depending on tumor location, internal mammary nodes may not be picked up. Even if there is no plan to go after the IM nodes, the review thought it still useful to know the drainage pattern of the tumor because it may have prognostic value.
2-10-12 entry Lymphatic drainage patterns from the breast http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1356216/?tool=pubmed open access (peri-lesional injection of tracer: a look at lymphatic drainage pattern according to location of breast tumor and may explain why mets to internal mammary chain occur even in the face of a negative axilla)
Incidence of internal mammary node metastases after a sentinel lymph node technique in breast cancer and its implication in the radiotherapy plan http://www.redjournal.org/article/S0360-3016%2804%2900655-8/abstract (peri-lesional injection of tracer: 14% of all patients found to have drainage to IM nodes with mets. Incidence ranges from a low of 4% in axillary node-negative tumors with tumor in the upper outer quadrant to a high of 72% in axillary node-positive tumors with tumor in the lower medial quadrant)
I'd also like to weigh in on this issue with my own spin. As someone who actually (ironically) does basic science research on vascular development in the context of normal and pathological angiogenesis (such as occurs in tumors), when I saw the large blood vessel light up on my diagnostic ultrasound even before my tumor biopsy, I knew things weren't looking good. I asked my oncologist if they would be doing CD31 (PECAM, blood vessel marker) IHC on my tumor sections and she said it wasn't performed, and wouldn't in any case change the course of treatment. However, given that TNBC is thought to disseminate through the vasculature as well as lymphatics, I wonder if this analysis would be a useful prognostic indicator of metastasis (see articles referenced below). I do agree with her however, in that ultimately, what we really want to know is how to kill those cells that have escaped the original tumor. Right now, we can only determine that empirically, which is not very satisfying from a scientific standpoint or from the veiw of the patient.
Cancer.2011 Dec 16. doi: 10.1002/cncr.26711. [Epub ahead of print]
The prognostic significance of lymphovascular invasion in invasive breast carcinoma.
Is this the type of stuff i was injected with a little while before they took me to surgery for my mastectomy? I was a little doped up and don't remember clearly what they told me.
Blair
Lump found 11/08 DX: 2/09 @52 TNBC L. Mast. 3/26/09, SN-, BRCA-, 4.5 cm (post surgical)T2NOMO Chemo: 4/09-10/09 Taxol x 12, A/C x 4, No rad.No recon. NED 1/17. New Primary right breast TN, 2/2018.
Turtle, I welcome you to post on the OPEN ACCESS thread. Neovascularization is a critical turning point in a tumor's path to increasing malignancy and metastatic potential, along with epithelial-to-mesenchymal transition (EMT) - both features are prominent in subtypes of TNBC. I had posted a timeline of molecular subtyping of TNBC earlier here that may be of interest to you. Charles Perou in your neck of the woods is the leading authority of molecular subtypes in TNBC.
On the doppler portion of my ultrasound, they noted "mild internal vascularity" and I wondered about neovascularization as well.
As I have discovered since starting down this path 2 months ago, there is a huge gap between what is known in the laboratory and what is the standard of care in clinical practice. Even if one knows everything that is to know in mice (not that we do) making that knowledge transferrable to humans is a tall order. Lots of good basic science groups are doing research in TNBC (the last frontier so to speak in BC) so I am hopeful that something groundbreaking (i.e. targeted therapy) will happen soon.
Novel staging system for predicting disease-specific
survival in patients with breast cancer treated with surgery as the first intervention:
time to modify the current American Joint Committee on Cancer staging system
TNBC is broken out as are a number of known prognostic factors: lymphovascular invasion and tumor grade.
Results based on a retrospective study from 1997 to 2006 at MDA and include patients who had surgery as the first intervention. Caveat on outcome: dates of inclusion largely predate the use of Herceptin for HER2+ disease.
Related articles:
Breast cancer prognostic classification in the molecular era: the role of histological grade
Very interesting. I remember that the Adjuvant Online stats that my oncologist showed me did include ER status, grade and lymph node status. Nothing about EGFR--I'm not sure that that is a standard test yet. But, at least there's progress, right?
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