Team ILC Warriors
Comments
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As someone who opted for Lx for my 1.1cm ILC, I'm curious about how many of the recent posters (those who had ILC that didn't appear on Mammo, US or MRI) have dense breast tissue? My ILC wasn't palpable but was seen on all three imaging modes - mammo, US and MRI. I don't have dense breast tissue. It has been described as either "mostly fatty" or "scattered heterogenous fibrous tissue". According to diagnostic guidelines, these two breast densities are the lowest and second lowest densities of the 4 point scale. Some state laws (including California where I live) require that all mammograms include a description of breast density. It is a major factor in whether or not any cancer (and especially ILC) is diagnosed or missed.
Did your ILC hide in dense breasts or are your breasts not so dense? How does your mammogram report describe your breast tissue? Don't know whether or not you have dense breasts? PLEASE ask your doc. And while you're at it, please get a copy of your mammogram reports if you haven't already. This is important info for every woman to know and especially for those with ILC history.
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MIne was very obviously a lump when I discovered it. My breast was hurting and I reached up and there it was!
xoxo Michelle
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I always had dense breasts but now on AI´s no longer dense.......
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Sunnyone - my breasts were also type "b" - scattered heterogeneous fibrous tissue. Even when I insisted that there was a lump, the radiologist would point to the mammogram image and say there's nothing there. It was only the last one where the radiologist compared the image to one from 3 years earlier that he could see a slight increase in density in one area. He showed it to me but they looked identical to me. His recommendation was that it was likely benign and that I should come back in 6 months, but at that point I had already made an appointment with the BS. The tumor turned out to be 5x4 cm. I have to say that before my dx I combed the Internet trying to find something that would help me understand why I could feel a lump that would be invisible on mammogram and US. I kept turning up pages about dense breasts, and knowing that my breasts were not dense was falsely reassuring - that I should not worry about this mass that could be felt but not seen. It was only after I got my diagnosis of ILC that I was able to understand how imaging would miss it. I think it's important to know your breast density, but I think any web site about breast health and imaging should also state that some breast cancers can't be detected by imaging no matter how dense your breasts are.0 -
Grandma3x - I wholeheartedly agree - mine was not seen on mammo or MRI, and after the mx the pathology showed multiple tumors in every quadrant of the breast and in the nipple.0
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Since I had mammos regularly and they were fine and the MRI was negative on my prophylactic side I don't have much faith in these tests. The doctor said my tumor must have been growing for quite a few years.
So glad to have had a BMX. BTW my breasts were moderately dense. Fibrocystic. They got sore lumps if I drank soy milk from the estrogen for years sowonder if that should have been a red flag
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I just had my diagnostic mammogram and sonogram today. The radiologist said that I am fine. I am happy but yet I am not reassured. I am concerned that ILC may be present but not seen on imaging. My ILC was pleomorphic. I will have an MRI in 6 months. An MRI reassures me more than a mammogram and sonogram does. At least there is close surveillance by my doctors.I have already had ILC and LCIS occur in a tumor that was previously biopsied and was thought to be benign. I had Invasive Tubular Carcinoma and LCIS in another tumor that was biopsied twice and both times I was told that this lump was benign. It was malignant.
I am still worried. I can't help it. I know that it sounds crazy but ILC is so sneaky, insidious, and scary.
Good luck to everyone here.
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i have refused mammograms ever since one failed to find the 5cm plus clearly visible to naked eye changes, and insist on an annual MRI. I hate them but they provide the best detail for ILC
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I still do the mammograms even though it almost useless and I also do MRI once a year.
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Sunnyone, my surgeon told me i had dense breasts, so the bmx was a wise choice given my previously undiscoverable 6+cm lesion. She said it was slow growing and probably had been growing for years. I was feeling bad that I had missed one mammo in 13 years.
I had been tossing and turning about my bmx decision for awhile when I asked her what she would do in my situation. She told me her breasts were so dense that her mammos are trash! They tell her nothing, but she would have a bmx in the same situation.
Unfortunately for us with Blue Cross/Blue Shield in Hawaii, we now have the dilemma where we have to have BCBS approve advanced imaging (MRI/PET). Only on weekdays during working hours. It's sad to be at the mercy of your insurance company to get a scan you need.
I have read that half of women have dense breasts, so what is really needed are better diagnostics. I had a DEXA bone density scan yesterday because I started anastrozole. The tech said that the 3D mammo is much better though a little more expensive (copay $70 vs $15) than a regular mammo. Has anyone had both and compared results?
614, each time I have had to wait for news through this ordeal, my mantra has always been "I am not going to worry about it until I have to." I know it is easier said than done, but if it is stress that may have contributed to this cancer, I am not going to add to that stress worrying about something that may or may not be there.
Rest easy, and cyberhugs to all!
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Last year the PA breast cancer coalition helped afvocate for a bill that was passed in October. Insurance companies must provide 3-d mammos for women with dense breadts
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My experience with ILC is similar. It did not show up on MRI or mammogram. Not only was the tumor almost 5cm, there were multiple tumors in every quadrant of my breast, and into the nipple. That being said, I will continue to do Annual mammos because there is the possibility that if there is cancer in the remaining breast, it might be ductal, and they would catch it. Also, because even though they missed the first one, they might not miss a second time. I would hope they may pay more attention to the results of a cancer survivor. In any case, I no longer worry about it. I intend to enjoy whatever life brings and every cancer free day is a good day that I intend to make the most of. I look at BC as just another condition I have to deal with. Hugs to all.
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Thanks to everyone here. I appreciate your posts.
I agree. I am glad that I will be getting annual MRI's. I will continue to have mammo's and sono's though because that is protocol/standard of care.
FYI: As I was about to get my mammo yesterday, I asked the technician if this was a 3D machine. (My breasts are heterogeneously dense so a 2D mammo is useless. My RO at M.D. Anderson Cancer Center in Houston, TX said that my breasts were among the most dense that he has ever seen.) She said, "No, this is a 2D machine." I insisted on having a 3D mammo (which costs $50.00 more). I ended up having the 3D mammo yesterday. The tech told me that a person must tell the scheduler that they want to have a 3D mammo at the time that the appointment is made or a 2D mammo will routinely be ordered. I did not know that. I am so glad that I happened to ask about the 3D machine.
Good luck everyone and thanks for your insight.
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Hello again -
Thank you for your valuable replies. Not exactly sure how initial post on breast density was taken to mean non-dense breasts = relax about imaging missing your ILC. Not at all.
Be vigilant, get all scheduled imaging and know the nature of your breast tissue.
Of further interest - check out this TED talk about gamma imaging - a test that detects 3 times more breast tumors and why it's not available to us. .....https://www.ted.com/talks/deborah_rhodes
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Very interesting TED talk on MBI. Thank you for sharing Sunnnyone22. I noticed there was an article in Breastcancer.org, titled Molecular Breast Imaging. Interesting read also. Most notably, it points out the radiation exposure is higher with the MBI vs MRI.
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As some of you have heard from me before, I was told all clear after both mammo and us about 8 months before I looked in the mirror and said, "Damn. I can see a lump right there" along with an inverted nipple that I had chocked up to getting older. The dense areas in both my breasts were in the upper halves for over 30 years. I did self exams, but wondered how I would ever be able to feel a distinct lump. Turns out, lobular doesn't usually form distinct lumps. There was no ILC found in my right breast, but was glad to have bilat mx to remove that worry.
A surgeon explained to me that lobular is radio-opaque because it is a fatty cell that blends in. It doesn't easily show up until it moves to tissue like bone, liver, etc. and decides to gang up. Also, at least in my case, because lobular is so indolent/slow growing, it produces a deceptively low SUV with PET. Same for why chemo can prove less effective.
I am so hoping that liquid biopsies/circulating tumor cell tests start providing reliable means of detecting lobular and that genomic testing can provide evidence of the effectiveness of a chemo before it is tried. Foundation One has just announced new tests along this line. http://www.businesswire.com/news/home/201605030069...
Best wishes for everyone!
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My ILC is mixed, both classic and pleomorthic cells. My oncologist assures me that that shouldn't worry me, well, it does, a little. I think what scares me the most that they will miss any possible mets, like they had missed the original cancer
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New ILC paper. Published May 2016.
Lobular breast cancer: Clinical, molecular and morphological characteristics.
Christgen M1, Steinemann D2, Kühnle E3, Länger F4, Gluz O5, Harbeck N6, Kreipe H4.
Author info:
1Institute of Pathology, Hannover Medical School, Hannover, Germany. Email: Christgen DOT Matthias AT MH-Hannover.de
2Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
3Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany.
4Institute of Pathology, Hannover Medical School, Hannover, Germany.
5Evangelic Bethesda Hospital, Breast Center Niederrhein, Moenchengladbach, Germany; West German Study Group, Moenchengladbach, Germany.
6West German Study Group, Moenchengladbach, Germany; Breast Center, University of Munich (LMU), Munich, Germany.Abstract:
Infiltrating lobular breast cancer (ILBC) is the most common special breast cancer subtype. This review provides a comprehensive description of ILBC characteristics, including epidemiology, clinical features, molecular genetics and histomorphology. Twenty detailed supplemental data tables guide through primary data of more than 200 original studies. Meta-analyses indicate that ILBC is at least twice as common in the Western world as it is in other geographic regions. ILBC is over-represented in so-called interval carcinomas and in primary metastatic breast cancer. ILBC is also associated higher age, higher pT stage and hormone receptor (ER/PR) positivity. Pathological complete response rates after neoadjuvant chemotherapy are low, ranging between 0% and 11%. Positive resection margins after breast-conserving surgery are comparatively frequent and 17% to 65% of patients undergo a second surgical intervention. Depending on the morphological stringency in the diagnosis of ILBC, lack of E-cadherin expression is observed in 55% to 100% of cases. CDH1/E-cadherin mutation detection rates vary between 12% and 83%. Various additional molecular factors, including PIK3CA, TP53, FOXA1, FGFR1, ZNF703 and BCAR4, have been implicated in ILBC or progression of lobular carcinoma in situ (LCIS) to invasive cancer and are discussed in detail. Eight instructive figure plates recapitulate the histomorphology of ILBC and its variants. Furthermore, we draw attention to rarely addressed histological details, such as two-sided nuclear compression and fat-avoiding growth at the invasion front. Last but not least, we discuss future translational research directions and emphasize the concept of synthetic lethality, which promises new options for targeted ILBC therapy.0 -
Darn. I can't use my old lab email address since being laid off and so can't access the full article. Does anyone have access and can specifically provide the info alluded to in the last sentence?
I'd also love to see what they say about the "fat-avoiding growth at the invasion front." The best explanation I have been given for ILC being radio-opaque is that the cells are closely akin to fat cells and so blend into the surroundings until they show up in different organs like bone and liver. I'm curious whether this new description is at all related.
You are such a purveyor of hope, John!
Sue
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This radio opaque issue worries me a lot............
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A friend accessed the article for me. I will cut and paste the last sections. Please refer to JohnSmith's last post for references.
11. The invasion front in ILBC A less frequently discussed histological detail of ILBC is the fatavoiding growth at the invasion front (Fig. 6). Targetoid infiltration of classical ILBC around mammary gland ducts and lobules has been described as "periparenchymal streaming" [270]. This term conveys that ILBC invasion is not massively destructive. Instead, the tumor cells appear to be inert, often elicit little desmoplastic reaction, float around preformed anatomical structures and, to some extent, even respect tissue borders. Mammary gland lobules are mostly embedded in connective tissue. A developing invasive ILBC is initially confined to this connective tissue and tumor growth follows the fibrous septa. Invasion seems to halt for a while at the border to the mammary fat. In these areas, single files of ILBC cells are aligned in parallel to the fat border (Fig. 6). Invasion into the fat appears reluctant. The fat-avoiding growth of classic ILBC may be related to adipose tissue-derived paracrine factors. Alternatively, it may just be another morphological expression of the same cellular behavior responsible for targetoid encircling of lobules. Whatever the mechanism, it is characteristic on the level of morphology and of some usefulness for histological subtyping.
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12. Mixed-type ILBC Histological subtyping can be problematic in cases with features intermediate between ILBC and BC of no special type. Accordingly, the terms ductolobular BC and mixed ductal/lobular BC are widely used and are recommended by the WHO, although there is no separate WHO classification code for this instance [238,239]. A quite variable proportion of BCs (3% to 70% of those with lobular features) has been found to belong to this category in different studies in the published literature (Supplemental Table 20) [15,99,138,233,273,292,293]. This implies a rather variable practice of histological subtyping in different diagnostics units. In our experience, truly chimeric cases are rare (<10% of BCs with lobular features). The traditional WHO definition of mixed ductal/lobular carcinoma is a mixture of 89% to 50% lobular growth pattern and 11% to 50% ductal growth pattern. As soon as the ductal growth pattern accounts for >50% of the tumor, classification as BC of no special type isWHO-compliant.As soon as the lobular growth pattern takes over atleast90%ofthe tumor, classificationas ILBCis recommended [238,239]. The practical application of this rules is not without problems. If two different tumor cell populations with clearly different growth pattern are present, the most likely diagnosis is collision of one ILBC and one BC of no special type. Immunohistochemistry may verify two biologically different tumor components with retained and lost E-cadherin expression, respectively (Fig. 7). Irrespective of the size ratio of the two components, these tumors should be termed collision tumors, at least for scientific purposes. Hormone receptor status and proliferation characteristics should be reported separately. Other BCs are homogenous, but lobular features are weakly developed. In these cases, quantification of a lobular and a ductal compartment is impossible and the WHO definition for mixed BCs is no longer applicable. Subtyping of such tumors should always include E-cadherinand -cateninorp120-cateninimmunohistochemistry. E-cadherin immunohistochemistry alone is a double-edged sword. As mentioned above, a positive immunohistochemical staining for E-cadherin does not rule out a functionally relevant mutation [145]. Additional stainings for -catenin or p120-catenin aim to assess E-cadherin functionality (also see section 5). Based on morphology and immunohistochemical characteristics, we seek to differentiate between (i) E-cadherinnegative ILBC with weakly developed lobular growth pattern, (ii) E-cadherin-positive ILBC with classic lobular growth pattern, (iii) E-cadherin-positive BCs of no specialtype with lobular-like growth pattern and (iv) BCs of no special type with decreased E-cadherin expression but no typical lobular histomorphology. Subtle morphological details, such as intracytoplasmic vacuoles, focal tubular structures or presence of LCIS foci, can turn the balance for the one or the other interpretation. Some attention should also be paid to the invasion front. E-cadherin-positive BCs of no special type with lobular-like growth pattern often display frank infiltration of the mammary adipose tissue (Fig. 8).
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And the conclusion:
13. Future directions Modern oncology aims to personalize cancer treatment. A prerequisite is the integration of clinicopathological information from various sources and methods. The most basic one is conventional histomorphology. ILBC is different from other types of breast cancer. This is evidenced not only by histomorphology, but also by epidemiology, clinical characteristics and molecular genetics. Optimization of ILBC therapy is catching up with other hot topics in the field [75,129]. A definite characterization of ILBC is particularly important in postmenopausal patients, in whom aromatase inhibitors and not tamoxifen are currently the first choice for adjuvant endocrine treatment. Within the next years, clinical trials will provide valuable information on potentially distinct response pattern of ILBC to different endocrine agents. Clinical trials will also provide newer data on the outcome of pleomorphic ILBC. Among the still unresolved questions in basic science is the putative origin of ILBC from a distinct mammary epithelial cell type or differentiation stage. Furthermore, cell biology research may discover new options for targeted ILBC treatment. Particularly promising is the concept of synthetic lethality. Two genes are synthetic lethal if inactivation of either one alone is tolerated, but simultaneous loss of both genes induces tumor cell death. In a proof-of-principle study, Guilford and co-workers have recently shown that synthetic lethality could be exploited for ILBC treat-ment. They successfully identified synthetic lethality targets in CDH1-deficient BC cancer cells. According to this study, lack of E-cadherin creates a vulnerability against pharmacological inhibition of certain G-protein-coupled receptors [294]. Hence, lack of E-cadherin expression could perhaps evolve from an immunohistochemical marker supporting histological subtyping into a druggable target. The possibility of tackling the Achilles' heel of ILBC could bring about tremendous changes in relevance of the histological subtype for BC diagnosis and treatment.
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I will try and find one of the pleomorphic threads to post this additional info from the article:
10. Pleomorphic ILBC Pleomorphic ILBC accounts for 1% to 5% of lobular carcinomas. Key histological features are bizarre nuclear pleomorphism, numerous mitotic figures and and slightly eosinophilic, granular cytoplasm, superimposed on a lobular growth pattern (Fig. 4). The irregular cell shaping combined with hyperchromatic, indented, compressed or elongated nuclei in eosinophilic cytoplasm can cause a rhabdomyoblastoid appearance [270]. The inter-observer concordance for pleomorphic ILBC is probably limited. However, a simplified definition of pleomorphic ILBC by a Bloom-Richardson score of 9 (upper range of histological grade 3) may still overestimate the frequency of these tumors [275]. In case of doubt, the diagnosis of pleomorphic ILBC should be reserved for carcinomas with exceptional cytological atypia and/or more objective molecular features, such as loss of E-cadherin combined with nuclear accumulation of p53 or overexpression of HER2. In fact, pleomorphic ILBC is increasingly perceived and defined as an entity that has escaped from the so-called low-grade molecular progression pathway associated with classic ILBC [212]. Lower rates of ER expression and activation/inactivation of additional oncogenes or tumor suppressor genes (p53, HER2 and others) argue for a transition to the high-grade progression pathway and for independence of ER-signaling (Supplemental Table 19) [166,175,211,275–281]. Interestingly, HER2 activation can result from amplification/overexpression or somatic mutation in these tumors [142,173–175]. Neither immunohistochemistry nor fluorescence in situ hybridization (FISH) can reliably detect HER2 activation by mutation. Current clinical HER2 testing guidelines do not mention this detail [282]. Further genes potentially involved in the transition to the high-grade progression pathway of pleomorphic ILBC include MYC, BCAR4, HIF1A and FER [218,283–285]. Pleomorphic ILBCs display complex genomic imbalances with numerous additional recurrent gains on chromosomes 8q24, 12q14, 17q12 and 20q13, superimposed on imbalances typical of classic ILBC (Fig. 4) [211,285]. The CpG island methylator phenotype proposed for classic ILBC is not preserved in pleomorphic ILBC [203,204]. Clonal evolution of classic ILBC can give rise to a secondary pleomorphic phenotype in recurrent and metastatic tumors [128]. In most other cases, escape from the low-grade progression pathway and acquisition of a pleomorphic phenotype seems to be an early event. This is evidenced by similar atypia and similarly complex molecular alterations in pleomorphic LCIS, LIN-3 with intraluminal necrosis and florid LIN (Fig. 5) [285–287]. In mammography screening core needle biopsies, isolated pleomorphic LCIS and LCIS with necrosis are thus regarded with much more suspicions than classic LCIS and are classified as a B5a lesion (in situ malignancy and obligate precursor of invasive cancer) in most countries, including Germany [288,289].
Looks like I might have to go begging my VA oncs to do further research on my last tumors...
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Thanks for posting this info. It saves me a trip to the hospital library.
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In terms of the "conclusion" and future translational research directions and the concept of "synthetic lethality", here's Dr. Guilford's Abstract from the recent 2016 AACR conference.
I believe he is only dealing with cell lines and hasn't started animal studies, so this approach may be a decade away. I hope I'm wrong.6. Abstract 3814: Synthetic lethal approaches targeting E-cadherin-deficient cancers
Tuesday, Apr 19, 2016, 1:00 PM - 5:00 PM
Augustine Chen1, Bryony J. Telford1, Andrew Single1, Henry Beetham1, Kaylene J. Simpson2, Parry Guilford1.
1University of Otago, Dunedin, New Zealand; 2Peter MacCallum Cancer Centre, Melbourne, AustraliaAbstract Body: E-cadherin is a cellular adhesion protein that is frequently mutated in lobular breast cancer and diffuse gastric cancer. The E-cadherin protein which is encoded by the CDH1 gene has key roles in establishing and maintaining cell polarity and differentiation, the organization of cell migration and architecture and the mediation of signaling through various proliferation and survival pathways. E-cadherin also has a tumor suppressor role and its loss in cancer cells would preclude drug targeting by conventional therapy. To circumvent this, we have taken a synthetic lethal approach to exploit any vulnerability created by the loss of E-cadherin. In the therapeutic setting, synthetic lethality refers to a combination of a mutated gene and a drug targeted at a second gene or protein causing cell death (specifically in cancer cells). To identify the vulnerabilities created by E-cadherin loss, we performed a genome-wide siRNA knockdown screen in isogenic MCF10A cell lines with and without E-cadherin expression. From the functional screen, we identified broad classes of G-protein-coupled receptor (GPCR) signaling proteins and families of cytoskeletal proteins which were highly enriched among the synthetic lethal candidates. Indeed, we identified drug classes with linkages to several of the GPCR and cytoskeletal targets that showed evidence of E-cadherin synthetic lethality when we performed a 4,057 known drug screen. These included certain PI3K inhibitors (PI-103), anti-glucocorticoid (mifepristone), tyrosine kinase inhibitor (saracatinib) and multiple histone deacetylase inhibitors (vorinostat and entinostat). Interestingly, the combination of saracatinib and mifepristone gave a synergistic effect (combination index < 1.0) in targeting E-cadherin-deficient MCF10A cells. These results demonstrate that E-cadherin loss creates druggable vulnerabilities that have the potential to improve the management of both of sporadic and familial lobular breast cancer and diffuse gastric cancer.
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It's a shame no one seems to be addressing the whole "it doesn't show up on scans" issue...
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Yes the not showing up in scans issue is a worry Sue................only MRI with contrast.......and then not always completely accurately. Its what makes lobular so scary as its so often discovered only when well established.
I cope by having circulating tumour cell tests done every year or two to try and get a little bit ahead of the game.......
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Lily - do you have to request those tests from your MO? I never heard of them.0
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Sunnyone22~
Thanks for posting the Deborah Rhodes TED Talk. Our health is connected to our knowledge as well as politics.
Dr. Rhodes' TT speaks to the discussion of imaging and density.
Highly recommended. One of the best speakers I've ever seen on TED
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