Spreadsheet: c32ffbe3-f961-4f68-8182-863ace05b1a4
Sheet: Sheet1

Detailed findings in PBSO studies on which analyses of occult serous cancers were based. | Unnamed: 1 | Unnamed: 2 | Unnamed: 3 | Unnamed: 4 | Unnamed: 5 | Unnamed: 6 | Unnamed: 7 | Unnamed: 8 | Unnamed: 9 | Unnamed: 10 | Unnamed: 11 | Unnamed: 12 | Unnamed: 13 | Unnamed: 14 | Unnamed: 15 | Unnamed: 16 | Unnamed: 17 | Unnamed: 18 | Unnamed: 19 | Unnamed: 20 | Unnamed: 21 | Unnamed: 22 | Unnamed: 23
Source Study | Genotype | Patient age | Histology | Serous histology for cals | Location | Stage | Stage for calcs | Size | Size for calcs | Grossly detectable | Recurrence | Study [NAME] | Cohort age - mean* | Included in prevalence calcs? | # [NAME] patients for prevalence | # occult serous cancers in BRCA1 patients for prevalence | # [NAME] patients for prevalence | #occult serous cancers in BRCA2 patients for prevalence | # BRCA- or indeterminate patients for prevalence | #of occult serous cancers in BRCA- or unspecified genotype patients for prevalence | Reason for inclusion in, or exclusion from prevalence calculation | Pathology work-up description | Notes
STUDIES WITH METICULOUS PATHOLOGY
[NAME], 2007 | BRCA2 | 44 | serous | 1 | FT | TIC | 0 | microscopic | microscopic | N |  | 60 | 43 | Y | 60 | 2 | 60 | 3 | 2 | 0 | Out of 122 women who had RRSO in the inteval studied, 60 each had BRCA1 or BRCA2 mutations and 2 had an unspecified BRCA mutation.   Thus any acertainment bias would have to be very small. | Either entire adnexa sectioned at 2-3mm intervals or SEEFIM protocol used (switched to latter about 3/4 way through the study).
[NAME], 2007 | BRCA2 | 66 | serous | 1 | FT | TIC | 0 | microscopic | microscopic | N
[NAME], 2007 | BRCA2 | 76 | serous | 1 | FT | IIIA | 3 | <1cm | 10 | Y
[NAME], 2007 | BRCA1 | 44 | serous | 1 | FT | TIC | 0 | microscopic | microscopic | N
[NAME], 2007 | BRCA1 | 62 | endometrioid | 0 | FT | I | 1 | microscopic | microscopic | N
[NAME], 2007 | BRCA1 | 61 | serous | 1 | FT | Ic | 1 | microscopic | microscopic | N
[NAME], 2007 | BRCA1 | 51 | endometrioid | 0 | FT | IIA | 2 | microscopic | microscopic | N
[NAME], 2004 | BRCA1 | 33 | endometroid | 0 | FT | Ia | 1 | 2.5mm | 2.5 | N |  | 58 | 46 | Y | 58 | 4 | 6 | 0 | 0 | 0 | Some of the genotyping was done after prophylactic surgery, but it seems that the testing was done irrespective of diagnosis. | Ovaries and FTs "entirely sectioned" but no sectioning interval specified.
[NAME], 2004 | BRCA1 | 49 | serous GII | 1 | FT | IIIb | 3 | 10mm | 10 | N | 20m
[NAME], 2004 | BRCA1 | 45 | "adenoca" GIII | 1 | FT and ovary | IV | 4 | 5mm | 5 | N | 11m
[NAME], 2004 | BRCA1 | 47 | serous GII | 1 | ovary | Ic | 1 | 8mm | 8 | N
[NAME], 2004 | BRCA1 | 37 | serous GII | 1 | ovary | Ia | 1 | not stated (microscopic) | microscopic | N
Laki et al, 2007 | BRCA1 | 46 | "adenoca" | 1 | FT | IA | 1 | Not grossly visible at surgery | microscopic | N |  | 56 | 48 | Y | 56 | 3 | 33 | 1 | 0 | 0 | It seems genotyping preceded counseling to undergo RRSO | "Systematic microsectioning and histopathological exam of serial sections of all ovary and FT tissues" | US exam in 46 women before SO, all normal.  CA125 in 39 women before SO, all normal.   Need to find out whether "cystadenocarcinoma" is compatible with serous.  (The term is sometimes used together with serous).
Laki et al, 2007 | BRCA1 | 55 | cystadenoca | 1 | ovary | IIC | 2 | Not grossly visible at surgery | microscopic | N
Laki et al, 2007 | BRCA1 | 53 | adenoca | 1 | FT | IA | 1 | Not grossly visible at surgery | microscopic | N
Laki et al, 2007 | BRCA2 | 54 | cystadenoca | 1 | FT and ovary | IIIC | 3 | Not grossly visible at surgery |  | N | metastatic disease
[NAME] et al, 2005 | BRCA2 | 50 | poorly diff serous | 1 | FT | Ia | 1 | 2.7mm & 1.7 mm | 2.908181412393031 | N |  | 43 | 47 | Y | 43 | 5 | 24 | 2 | 0 | 0 | Genotype preceeded RRSO | Entire ovaries and FTs examined at 2mm sectioning interval. | 2 patients who did not have detectable occult cancer developed peritoneal CA within 5 yrs after RRSO - neither was in compulsive protocol group (vs. 100% of patients with occult cancers). Stages inferred from description in paper.
[NAME] et al, 2005 | BRCA2 | 53 | HG serous | 1 | FT | Ia | 1 | 12 mm | 12 | Y
[NAME] et al, 2005 | BRCA1 | 52 | HG serous | 1 | FT | Ic | 1 | 2.2 mm | 2.2 | N
[NAME] et al, 2005 | BRCA1 | 42 | HG [NAME] serous | 1 | FT | CIS | 0 | microscopic | microscopic | N
[NAME] et al, 2005 | BRCA1 | 49 | poorly diff serous | 1 | ovary | Ia | 1 | 0.9 mm | 0.9 | N
[NAME] et al, 2005 | BRCA1 | 54 | HG serous | 1 | ovary | Ia | 1 | microscopic | microscopic | N
[NAME] et al, 2005 | BRCA1 | 54 | mod diff serous | 1 | ovary | Ia | 1 | microscopic | microscopic | N
[NAME], 2006 | BRCA1 | 48 | HG serous | 1 | peritoneal | IIIC | 3 | disseminated pelvic disease, bulky | 100 | Y | persistent | 40 | 47 | Y | 40 | 5 | 22 | 1 | 0 | 0 | 24 of 113 women were not tested.  If the fraction of BRCA1 positive women in the untested group was the same as in the tested group, there would actually have been 51 BRCA1+ women in the study group.  Of the cancers, 5/6 cancers in genotyped women were BRCA1+.  If we assume that the untested woman with cancer has an 83% probability of being BRCA1+, then the prevalence of occult cancer in BRCA1 women is 11.4% (5.83/51), if we exclude the untested women, the directly calculated prevalence is 12.5% (5/40).  If we assume that the untested woman has only a 45% chance of being BRCA1+ (i.e. same as fraction of all genotyped women), then prevalence is 5.45/51=10.6%. | "complete sectioning of fallopian tubes and ovaries" at 2-3 mm intervals, so qualifies as meticulous. | stages inferred from description in paper; (4 previously in Leeper 2002); Median 28 months follow up
[NAME], 2006 | BRCA1 | 47 | HG serous | 1 | FT | IC | 1 | "microscopic" CIS 8mm [NAME] | 8 | N
[NAME], 2006 | BRCA1 | 62 | HG serous | 1 | FT | IC | 1 | "microscopic"  7mm [NAME] | 7 | N | 17mo
[NAME], 2006 | BRCA1 | 52 | HG serous | 1 | FT | CIS | 0 | "microscopic" CIS | microscopic | N
[NAME], 2006 | BRCA1 | 46 | HG serous | 1 | FT | CIS | 0 | "microscopic" CIS | microscopic | N
[NAME], 2006 | BRCA2 | 65 | HG serous | 1 | FT | CIS | 0 | "microscopic" CIS (<1cm) | microscopic | N
[NAME], 2006 | unknown | 48 | borderline | 0 | ovary
[NAME], 2006 | BRCA1 | 44 | serous | 1 | FT | CIS | 0 | 2 | 2 | N |  | 6 | 55 | N |  |  |  |  |  |  | Description unclear - the study was initiated "following the discovery" of an occult fimbrial cancer in a BRCA (not specified) RRSO specimen.  This is referred to as the "index case", which suggests that it might be included in the reported cohort.  Since the one serous cancer in a BRCA1 patient was in the ampulla and not the fimbria, it cannot be the index case.  So the prevalence of occult serous cancer in BRCA1 women in this study is either 1/5 or 1/6 (depending on whether we assume that the other BRCA1 woman was the index case).  For BRCA2 it's either 2/6 or 3/7, depending... Probably should not be called prospective (authors say this study can't be used to estimate prevalence, since it was initiated with index case). | Either serial sectioning at 2-3mm intervals with complete sectioning of fimbrae (7/26 patients), or SEEFIM protocol (19/26 patients).   The 26 patients included 6 BRCA1 positive and 7 BRCA2 positive RRSOs, and a control set of 13 non-BRCA-mutated patients undergoing salpingo-oopherectomy (typically TAH) for other indications (cervical or endometrial).  From description, sounds like all cancers were only diagnosed histologically, not grossly, but they never say this explicitly.  (In two cases it's completely clear that they were not grossly visible, since they were even missed on the first microscopic exam).
[NAME], 2006 | BRCA1 | 62 | endometroid | 0 | FT | I | 1 | 7 | 7 | N
[NAME], 2006 | BRCA2 | 76 | serous | 1 | FT | advanced | 3 | 1.2 | 1.2 | N
[NAME], 2006 | BRCA2 | 66 | serous | 1 | FT | CIS | 0 | 1 | 1 | N
[NAME], 2006 | BRCA2 | 43 | serous | 1 | FT | CIS | 0 | 1 | 1 | N
STUDIES WITH NON-METICULOUS PATHOLOGY
Finch et al, 2006 | BRCA1 | 42 | HG serous | 1 | FT | Ib | 1 | 15mm | 15 | Y |  | 94 | 47 | Y | 94 | 6 | 65 | 1 | 0 | 0 | Note: the 159 patients in this study included 60 patients (including 38/39of the [NAME] or BRCA2 carriers) in the previous Colgan et al study.  "a small number of patients" in this study were genotyped after surgery.  [NAME] toward (or against) genotyping patients with occult cancer not noted.  Probably OK (but not perfect) to include in prevalence calculations.  Need to segregate from the Colgan patients. | From Jan 1992-2000, (68 patients) only representative sections of FT's examined.  From 2000-June 2004 (91 patients), both FTs and ovaries were sectioned and microscopically examined "in their entirety" (not specified in greater detail). | All but one of 39 patients from Colgan 2001 are included here - so 2/67 additional BRCA1 patients had cancer - patients reported in Finch are not included in the list for Colgan  All but one (the 59 yo in Colgan) had negative ultrasound between 1 and 9 months prior to RRSO (average 5).  4 of 7 had CA125 average of 4mo earlier, all negative.  [Since the ascertainment is clearer for Finch,  tumors overlapping with the Colgan study are listed here and removed from the Colgan list].  (called oopherectomy, but from the description appears to include FTs).
Finch et al, 2006 | BRCA1 | 44 | HG serous | 1 | FT | IIa | 2 | 1.6mm | 1.6 | N
Finch et al, 2006 | BRCA2 | 53 | NS - primary peritoneal | 1 | peritoneal |  | 3 | 1mm (largest focus) | 1 | N
Finch et al, 2006 | BRCA1 | 40 | HG serous | 1 | ovary | Ia | 1 | < 1mm | 1 | N
Finch et al, 2006 | BRCA1 | 48 | HG serous | 1 | FT and ovary | IIb | 2 | 50mm | 50 | Y
Finch et al, 2006 | BRCA1 | 59 | HG serous | 1 | FT and ovary | IIc | 2 | not specified 4 "foci" - not grossly visible | 3.1748021039364 | N
Finch et al, 2006 | BRCA1 | 64 | HG serous | 1 | FT | CIS | 0 | microscopic | microscopic | N
[NAME], 2006 | BRCA1 | 73 | HG serous | 1 | ovary | IIIC | 3 | <15mm | 15 | Y | 72 mo | 37 | 50 | Y | 37 | 6 | 13 | 0 | 0 | 0 | Prospective - genotyping carried out before PO | Not meticulous.  20/50 complete sectioning of ovaries and tubes, the rest only partial examination,  all but one of these tumors wwas surgically occult and discovered only during microscopic examination - but the paper doesn't say which of the  tumors was grossly evident.  (So I labeled one of the larger tumors as grossly detectable, arbitrarily chosen). | 44 of the 50 total patients had BSO.  The rest had either bilateral oopherectomy (3) or unilateral SO.
[NAME], 2006 | BRCA1 | 46 | HG serous | 1 | ovary | IIIC | 3 | <15mm | 15 | N
[NAME], 2006 | BRCA1 | 42 | HG serous | 1 | FT | IIB | 2 | 3mm | 3 | N | 19 mo
[NAME], 2006 | BRCA1 | 49 | CIS | 1 | FT | CIS | 0 | <4mm | 4 | N
[NAME], 2006 | BRCA1 | 61 | CIS | 1 | FT | CIS | 0 | <4mm | 4 | N
[NAME], 2006 | BRCA1 | 48 | CIS | 1 | FT | CIS | 0 | <4mm | 4 | N
Colgan et al, 2001 | BRCA1 | NS | HG serous | 1 | FT | NS | 1 | microscopic | microscopic | N |  | 27 | NS | N |  |  |  |  |  |  | Genotyping was either before or after surgery and was not performed on all patients, so there might be a bias toward BRCA1 genotypes documented in patients with cancer as opposed to those without, if diagnosis affected decision to get genotyped.  Note that most of the patients in this study were also among the patients in the Finch et al. 2006 gyne onc study.  (overlaps with Finch et al 2006 gyne onc. data on this sheet are deleted from this listing for [NAME] 2001). | For 20 of the 60 cases in this study, the fallopian tubes were completely sectioned and examined.  For 40 of the cases only "representative" samples were embedded and sectioned.  So mostly not "meticulous".  Note that the procedure was called "oopherectomy" but in fact was BSO.
[NAME] et al, 2000 | BRCA1 | 49 | HG serous | 1 | FT and ovary | IIA | 2 | 1 mm several foci | 1.587401051968199 | N |  | 18 | 46 | Y | 18 | 1 | 1 | 0 | 0 | 0 | For prevalence calculation: 18 of the BRCA1+ women were genotyped pre-operatively, one of these had a cancer detected on PBSO. So could use 1/18 as the prevalence.  1 of the BRCA2 women was genotyped pre-operatively and she didn't have cancer (the one with cancer was a post-op genotype). | According to the description in the paper, 18/20 of the BRCA1 patients were identified pre-operatively.  2/20 were identified after an occult cancer was discovered at PO. Thus, the prevalence should be inferred to be 1/18.  In 37 of the 50 total cases (diagnosed at [NAME]), ovaries and FT's were entirely sectioned at 2-3mm intervals.  In the rest (diagnosed at outside hospital and reviewed at [NAME]), they were "not entirely sectioned" but no further description provided. Called oopherectomy but actually BSO. | Size for calcs is diameter of equivalent sphere of sum of volumes.
[NAME] et al, 2000 | BRCA1 | 40 | borderline | 0 | ovary |  |  | 8-10 mm | 10 | Y
[NAME] et al, 2000 | BRCA1 | 49 | borderline | 0 | ovary |  |  | 4 mm | 4 | N
[NAME] et al, 2000 | BRCA2 | 65 | HG serous | 1 | FT and ovary |  | 1 | 2mm and microscopic | 2 | N
[NAME] et al, 2000 | BRCA1 | 63 | serous | 1 | FT | Ic | 1 | <7mm | 7 | N |  | <29 | NS | N |  |  |  |  | 29 | 4 | 4 of the patients with occult cancers (bold) were from a series of 29 RRSOs at UW between 1996-2001. | Complete sectioning at 3-4mm intervals - not meticulous - will miss some,but better than most. | Since the denominator (29 consecutive patients) didn't distinguish genotypes, the 4 patients in this group found to have occult cancer are listed in the indeterminate group even though they actually have known genotypes.
[NAME] et al, 2000 | BRCA1 | 47 | serous | 1 | FT | Ic | 1 | <8mm | 8 | N
[NAME] et al, 2000 | BRCA2 | 65 | serous | 1 | FT | Ia | 1 | 2mm | 2 | N
[NAME] et al, 2000 | unknown | 74 | serous | 1 | FT | If | 1 | 4mm | 4 | N
[NAME] et al, 2000 | unknown | 43 | serous | 1 | FT | If | 1 | 9mm | 9 | Y
[NAME] et al, 2000 | BRCA1 | 48 | serous | 1 | peritoneal | IIIc | 3 | multiple <5mm | 10 | Y
NS = Not specified
* when mean age was only given for entire series, irrespective of genotype, we assumed that the mean age for the BRCA1 women in the series was the same as the overall mean.
STUDIES EXCLUDED | Reason for exclusion |  |  |  |  |  |  |  | Citation
Finch, 2006** | Tumor histology not specified. No description of pathology protocol provided |  |  |  |  |  |  |  | Finch A, Shaw P, Rosen B, Murphy J, [NAME], et [NAME]. (2006) Clinical and pathologic findings of prophylactic salpingo-oophorectomies in 159 BRCA1 and BRCA2 carriers. Gynecol Oncol 100: 58-64.
Kauff, 2002 | Tumor histology not specified |  |  |  |  |  |  |  | Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, et [NAME]. (2002) Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346: 1609-1615.
Leeper, 2002 | All 5 of the patients in this study were included in Lamb et al 2006. |  |  |  |  |  |  |  | [NAME], [NAME] R, Swisher E, Goff B, Greer B, et [NAME]. (2002) Pathologic findings in prophylactic oophorectomy specimens in high-risk women. Gynecol Oncol 87: 52-56.
[NAME], 2001 | Anecdotal, no denominator. |  |  |  |  |  |  |  | [NAME], Swisher [NAME], [NAME], [NAME], [NAME], et [NAME]. (2001) Occult cancer of the fallopian tube in BRCA-1 germline mutation carriers at prophylactic oophorectomy: a case for recommending hysterectomy at surgical prophylaxis. Gynecol Oncol 80: 176-180.
Rebbeck, 2002 | Procedure was "prophlyactic oopherectomy" - not salpingo-oopherectomy. Retrospective study design (potential bias in genotyping positive POs) |  |  |  |  |  |  |  | Rebbeck TR, [NAME], Neuhausen SL, Narod SA, Van't [NAME], et [NAME]. (2002) Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346: 1616-1622.
Scheuer, 2002 | Tumor histology not specified |  |  |  |  |  |  |  | Scheuer L, Kauff N, Robson M, Kelly B, Barakat R, et [NAME]. (2002) Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. J Clin Oncol. 20(5):1260-8