genetics of ILC study

I am happy to participate - I only fall into the under 45 group. I just sent my email off!

I also received an email a couple of days ago and will be receiving the packet. I'm looking forward to participating in this.

Rue

me too!

I'm going to "play" too...awaiting the packet...we'll have to start a "pack-et rat" thread

Valerie--I wish they would do a study that included looking into how often LCIS goes on to become ILC.  I was diagnosed with LCIS 4 years ago, my mom is nearing 21 years as a survivor of ILC.

Well,there is the Li et al SEER study (2006)



"among LCIS patients, incidence rates were 7.3/1000 person-years and 5.2/1000 person-years, respectively. LCIS patients were 5.3-fold more likely than DCIS patients to develop invasive lobular carcinomas." http://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=12353815



Here are exerpts from the actual article. The tables don't convert. Here is a copy of the relevant table, but its really hard to figure out due to the layout.



Table 3. Risk of Ductal and Lobular Invasive Breast Cancer Among Women Diagnosed With LCIS (n = 4270; 21,582 Person-years at Risk) Compared With Women Diagnosed With DCIS (n = 24,187; 110,560 Person-years at Risk)*


________________________________________
Histology of the Invasive Cancer Invasive Cancers Diagnosed Among Women With DCIS
________________________________________ Invasive Cancers Diagnosed Among Women With LCIS
________________________________________
No. of Cases % of Total HR
95% CI No. of Cases % of Total HR
95% CI
________________________________________
Ductal 799 87 1.0 ref 123 51 0.8 0.7-1.0 Lobular 120 13 1.0
ref 119 49 5.3 4.1-6.9
________________________________________
* Excluding both DCIS and LCIS patients treated with a total mastectomy.
All hazard ratios (HR) are adjusted for age, year, registry, race/ethnicity, and surgery.
P < .05We examined the effects of DCIS features on the risk of subsequent ipsilateral and contralateral breast cancer separately. Compared with women diagnosed with DCIS at age 50-59 years, women diagnosed at 20-49 years of age had an elevated risk of ipsilateral invasive breast cancer (Table 4). With respect to race/ethnicity, blacks with DCIS had increased risks of both ipsilateral and contralateral breast cancer compared with non-Hispanic whites. Women with comedo, papillary, and solid DCIS had modest increased risks, whereas women with cribiform DCIS had a reduced risk of ipsilateral breast cancer compared with women with DCIS NOS, though only the risk associated with comedo DCIS was statistically significant. Women with solid DCIS also had an elevated risk of contralateral breast cancer, but, again, this risk was within the limits of chance. Finally, compared with women with well differentiated DCIS, women with poorly differentiated DCIS had an elevated risk of ipsilateral, but not of contralateral, invasive breast cancer. "



Here is an exerpt of the discussion section of this paper regarding LCIS.



"DCIS is generally considered to be a precursor lesion for invasive breast cancer, whereas LCIS is typically thought of as a nonsurgical disease that is viewed as a risk factor for, but not a precursor of, invasive breast cancer. Our observation that women with LCIS are 5.3-fold more likely to develop invasive lobular cancer (ILC) and 0.8-fold less likely to develop invasive ductal carcinoma (IDC) compared with women with DCIS, may lead one to question the latter description. These results are also consistent with a previous report indicating that LCIS is often followed by ILC,[29] and suggest that LCIS may be a precursor of ILC specifically, as one might expect based on its histopathologic characteristics. There is laboratory evidence to support this. E-cadherin is a cell adhesion molecule that is not expressed by almost all ILCs, but this molecule is expressed by almost all IDCs. Acs et al.[30] found that 96 of 100 (96%) IDCs expressed e-cadherin, whereas 41 of 42 (98%) ILCs showed complete loss of e-cadherin expression. Similarly, 128 of 131 DCIS (98%) cases expressed e-cadherin, whereas 50 of 53 LCIS (94%) cases had complete loss of e-cadherin expression. Thus, e-cadherin not only distinguishes lobular from ductal carcinomas, but also loss of its expression appears to be an early event in the development of lobular carcinomas. So there is growing evidence suggesting that LCIS may be a precursor of ILC, rather than just a marker of invasive breast cancer risk.



One of the reasons for our observation that women with LCIS have a higher incidence rate of invasive breast cancer, and particularly of ipsilateral invasive breast cancer, may be because LCIS has been historically viewed as a nonsurgical disease and, thus, often not treated definitively. This is largely due to results of several studies published from 1974 to 1991 that were based on cohorts of LCIS ranging in size from 34 to 258 cases, with 6 to 54 incident invasive breast cancers. These studies found that women with LCIS were equally likely to be diagnosed with ipsilateral and contralateral invasive breast cancers. Thus, it has been argued that the only logical operation for LCIS would be a bilateral mastectomy, which would be unnecessary approximately 75% of the time.[17] Our results challenge this notion, as we actually found that incidence rates of ipsilateral invasive breast cancer were higher among LCIS patients compared with DCIS patients (7.3/1000 vs. 5.4/1000, respectively), whereas rates of contralateral invasive breast cancer were more similar between LCIS and DCIS patients (5.2/1000 vs. 4.5/1000, respectively). The reason for these differences may be that DCIS patients are more likely to have definitive local surgical treatment than are LCIS patients. Specifically, it is striking that only 95 of 4046 (2%) LCIS patients in this study who received a partial or less than total mastectomy also received radiation, whereas 12,804 of 23,687 (54%) DCIS patients who received a partial mastectomy were treated with radiation. Clearly, LCIS patients are routinely not receiving definitive local treatment, but, based on our study, it appears that these women have a higher incidence rate of ipsilateral invasive breast cancer than of contralateral breast cancer, contrary to what has been reported previously. Thus, local treatment for women with LCIS may be warranted, although further studies are needed to evaluate this.



In summary, this study provides greater insight into the clinical significance of DCIS and LCIS over a recent time period in which the incidence rates of these two lesions has increased dramatically.[1] With respect to DCIS, our results suggest that screening women diagnosed with DCIS at a young age more frequently may be one way to reduce their risk of subsequent advanced-stage breast cancers. Furthermore, improving follow-up and screening of black women and Hispanic white women with DCIS may be an important means of reducing their risks of advanced-stage invasive breast cancer. With respect to LCIS, our data indicate that LCIS may be a precursor lesion of ILC rather than just an ambiguous risk factor for invasive breast cancer and that localized treatment for LCIS may be warranted given that these women have much higher rates of ipsilateral invasive breast cancer, but much more similar rates of contralateral breast cancer, compared with DCIS patients. Given that there are a growing number of women who have been diagnosed with DCIS and LCIS, continued investigations of these tumors are needed to better understand their etiology and to determine what treatments may be most effective for improving overall and disease-free survivals of these women.

I certainly hope they do more studies too.

Yipee! I found an on-line free copy of the Li article.



This Li study obviously has some caveats-they didn't follow which LCIS patients had a family history, took hormones or AIs, or how consistently they were diagnosed, etc. That being said,



The enigmatic Table 3 in the article lists for LCIS patients who subsequently got invasive breast cancer 1988-2001

(n=4270 women, 21,582 person-years risk)


I'm having formatting problems again....


LCIS women got 123 ductal cancers (51% of the total number of invasive cancers) with a 0.8 Hazards ratio and CI of 0.7-1.

This same LCIS group also got an additional 119 lobular cancers (which is 49% of the total number of invasive cancers) with a hazards ratio of 5.3 and confidence interval of 4.1-6.9.




This excluded LCIS patients that were treated with mastectomy.

Hazards ratio was adjusted for age, year, registry, race/ethnicity, and surgery.

Confidence interval P is less than 0.05 (sorry I cannot get a 'less than' sign to appear here without cutting out the 0.05 number)... more formatting problems.....


And, unlike the DCIS cohort, the tables don't say what stage of invasive bc the LCIS women got.




http://www3.interscience.wiley.com/cgi-bin/fulltext/112579964/PDFSTART



By the way, the way I found this article was *not* to do a Pubmed search, but to do a Google search, then for *some* publishers there is a link that can link you to a full text version.
I have LCIS + ALH.

I'm so sorry you are going through this anxiety.



The studies I've read seem to imply that LCIS may be a non-obligate precursor, at least in some cases. Obviously, not all LCIS patients go on to get bc.



My mammo and US (9-07) was 'fine'. They only did my L breast (where I have had all my issues.) This is the first time I had *no* interaction with the radiologist, so I couldn't show her the Port paper about MRIs. The tech said this was followup for my 2-07 biopsies.



Then I get a letter from the rad saying that the recommend a mammo in a year,' this will put me back on track.'



What kind of track is that? No MRI, not even a baseline. This will mean that my R breast will go 1.5 years without a mammo. I will be having a discussion with my onc in Nov.



I frankly feel betrayed. Why don't they tell me directly how crummy their predictions are? The Gail model is little better than a coin toss, and if the Gail model is that bad, you know their prediction for LCIS women will be a lot worse than that. The ACS MRI paper is internally inconsistent with regard to LCIS. And the rad recommendation isn't even giving me yearly mammos.



The only other LCIS study of any size with any details is the Port study. (I have *not* looked at all LCIS studies, but this Port study has one of the bigger groups, though of course much smaller than the Li et al study.)



***However, it doesn't say what kind of invasive cancer was diagnosed (ie ILC or IDC.)****



It looked at 126 atypical hyperplasia and 252 LCIS women. About half of them chose to be followed by MRI and half didn't. This may be a more homogeneous group since it all took place at the same institution (Sloan-Kettering), and the may have used more consistent definitions of AH and LCIS. All patients were followed with yearly mammos, and twice yearly clinical exams.



I know the formatting won't turn out again, so its difficult to describe the two groups side by side.

The MRI population had

(n=182). LCIS 135, Atypia 47, mean age 52 (25-74), Premenopausal 68 (37%), Family history (1 or more first degree relatives with breast cancer) 64 (35%), Tamoxifen/raloxifene 51 (28%).



The no MRI population had

(n=196, LCIS 117, Atipia 79, mean age 59 (33-90), Premenopausal 39 (20%), Family history 47 (24%), Tamoxifen/raloxifene 41 (21%).



I will use the following abbreviations:

fh=family history (first degree relatives with bc)



post=postmenopausal

pre=premenopausal

Peri=perimenopausal

t/r=tamoxifen/raloxifene

ts=tumor size, cm

lymph node status=lns



The description of the patients who were diagnosed with breast cancer (April 1999 to July 2005).

Non MRI group:

Patient number

1, Atypia, age 56, post, no fh, no t/r,ts 4, lns+, birads mammo 5

2, LCIS, age 62, post, no fh, t/r,ts 0.4, lns-, birads mammo 4

3, LCIS, age 59,post, no fh,t/r,ts1,lns+, birads mammo 4

4, LCIS,age 88, post, unknown fh, no t/r,ts 1.3, lns+, birads mammo 4

5, Atypia, age 61, post, no fh, no t/r,ts 0.7, lns-, neg/palpable mass

6, LCIS, age 55, peri, no fh, t/r, ts1.2 (Lt), dcis (rt), lns -, neg/palp mass lt and mammo birads 3 (rt)

(Patient presented with an interval palpable mass after recent negative MRI and mammo.)

7, LCIS, age 50, peri, no fh, no t/r, ts 0.7, lns-, birads mammo 4.





For the MRI screened group:

patient number

1, LCIS, age 43, pre,0 fh, no t/r, ts 0.9, lns-, birads mammo -, birads MRI 4.

2, LCIS, age 43, pre,0 fh, no t/r, ts 0.2, lns-, birads mammo -, birads MRI 4.

3, LCIS, age 51, peri, 0fh, no t/r,ts0.7 (lt) and 0.65(rt), lns-, birads mammo - (bilaterally), birads MRI 4 (bilateral)



4, LCIS, age 55, post, 1 fh, no t/r, ts DCIS, lns not done, birads mammo -, birads MRI 4.

5, LCIS, age 39, pre, no fh, no t/r, ts DCIS, Ins not done, birads mammo -, birads MRI 4.

6, LCIS, age 49, pre, 1 fh, no t/r, ts 0.35, lns -, birads mammo -, birads MRI 4 (bilateral)

Patient found to have cancer incidentially on a risk-reducing mastectomy.

7, Atypia, age 57, post, no fh, no t/r, ts 2.5, lns+, birads mammo -, birads MRI -.

(patient presented with an interval palpable mass after recent negative MRI and mammo.)



http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17206485&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Thank you so much, nash. I really respect my ILC sisters.



I don't know hardly anything about pleomorphic LCIS (PLCIS). and had no idea it could invade the pectoralis muscle.



I am so sorry this happened to you.



Thank you so much for sharing what happened to you, and for your support. There is so very much that is unknown.

I do remember this paper where they were trying to treat LCIS with excision and radiation. This paper is from Reims, France in 2005. I know these are small numbers of patients, but thought you might be interested.



Lobular carcinoma in situ (LCIS) is generally treated by conservative surgery alone and less often by mastectomy. We report our experience using conservative surgery and whole breast irradiation (WBI) for the treatment of patients with LCIS. From 1980 to 1992, 25 women with a median age of 54 years underwent lumpectomy (20) or quadrantectomy (5) and WBI (median dose: 52 Gy) for treatment of their LCIS. Five cases had palpable lesions, 19 were found by mammography alone and one case was found due to nipple discharge. Twelve women received tamoxifen at 20 mg/day for 2 years. With a median follow-up of 153 months (range 58-240), only one local recurrence was observed. The global rate of bilateral carcinoma was 17.6% (two synchronous and one metachronous). Until now, no case of LCIS treated by lumpectomy and radiation therapy has been reported in detail in the literature. After biopsy alone for LCIS, a subsequent infiltrating carcinoma occurs in approximately 15% of cases. Thus, classical radiosurgical therapy should represent an interesting alternative both for limited surgery alone and mastectomy, both of which have been proposed as sole treatments for LCIS.

Leaf---I'm so glad to hear you got good results from your recent mammo and US. I finally heard from my oncologist Tues.--he feels my MRI findings are most likely benign ("97% benign"), but knows I don't like the "wait and watch" routine, so he is letting me go for bilateral ultrasounds on Friday. I really thought I would have to push for them, but he offered them readily. I told him I'm certainly not out looking for trouble, I don't want any unecessary biopsies, I just want peace of mind. If  the US shows something more suspicious, then I will certainly insist on biopsy. I don't understand why they would only check the breast you had the problems with when both breasts have equal risk with LCIS.  All my tests  have always been performed bilaterally due to the equal risk. (I did question my onc about it once when he mentioned a mammo for just one side, I said "shouldn't they  always check both sides due to the fact that LCIS is most often found bilaterally? and he agreed and now has always remembered to send me for bilateral imaging). It did take me almost 3 years to get him to send me for MRI as he was concerned about false findings, but I think he realizes that I'm willing to take that risk in order to stay on top of this situation and find anything earlier rather than later when it's more difficult to treat.
 

Did you notice they finally gave us our own LCIS catagory!

I got the blood tubes on Wednesday sent Fed Ex.  Luckily, I had an onc appt Thursday with blood work so I took them then.  They were happy to fill the tubes for me and then I dropped them back in the Fed Ex box on the way home. Couldn't have been easier!

Just sent off my email, thanks for the heads up-

Susan