Monitoring ovarian cancer following chemo

Dear Cathy –

According to the NIH study cited below, YES, Ovarian cancers can be HER2 positive.  This is quite a long article and rather than try to pick out the highlights, I would just reference the article.  You might want to print it out, high lite the parts that peak your interest and talk it over with your oncologist.  Not many queries on this site talk about the “Human Epidermal Growth factor Receptor”.  It is a gene that was first thought to be found only in Breast Cancer patients.  But then it was also found that many Esophageal Cancer patients were also presenting with this over-expressive oncogene.  And Herceptin has been found to curtail the rapid reproduction of that particular cancer gene.  So the FDA has approved the use of Herceptin in both Esophageal and Breast Cancer patients.  And now I see that it has also found to be present in Ovarian Cancers as well.  I’m certainly not qualified to comment intelligently on this long study, but it seems to answer your question.  In the abstract it states that this is a study of advanced Ovarian Cancer patients.

It seems that once we have been diagnosed with cancer of any kind, one “lingering” concern is, “Am I really cured or just in remission, and where might it rear its ugly head next?”  But we can’t fixate our minds on that possibility sometime in the future, to the point that it cripples us in our daily routine of life.  We mustn’t let the uncertainties of the future keep us from enjoying things that we still do in the here and now.  Cancer surely makes us more appreciative of life, our loved ones, and the importance of fulfilling our God-given mission in life.

As for my follow-up routine, when I’ve been on active treatments, which by now are quite a few, my oncologist will usually perform a PET/CT to ascertain the degree of cancer present.  Heretofore, my chemo treatments have been Carbo/Taxol on 3 different regimens.  He always performs a CT scan after the 3^rd of 6 scheduled treatments to see the effectiveness of the drug. 

However, since I am Stage IV and have blood clots, I go weekly for lab work and an INR check.  Every 3^rd week, I also have a CA-125 count done.  Then the 4^th week, I have the usual blood work done and have a “one-on-one” consult with my oncologist.  So I’m constantly going in for “check-ups”.  So pretty much, I would say I go to see my oncologist on a monthly basis.  Even though my tumor markers are on a rapid rise, since I’ve already had 3 different treatment regimens of the Carbo/Taxol, the oncologist thinks perhaps we should go to something else.  But I’m not for “staying alive” at any price!  Quality of life is my goal.

Right now although the markers are rising, except for fatigue that plagues us all, I’m feeling too good to subject myself to another round of any drug, be it a repeat of what I’ve had or something new.  I know that up until now, I’ve been receptive to this platin combo, and that is good. But lately, it seems that it isn’t keeping the cancer stable for as long as he, or I would like.  This indicates that I am becoming platin resistant, and that its effectiveness is not as great as it once was.  Still I’m thankful for the quality of life the treatments have afforded me.  Of course, any little new feeling or sudden pain makes me wonder “where did this come from—what’s happening now?” 

As most realize, with a Stage IV diagnosis, the aim is for a “progression free survival” (PFS) time.  I’m aware that there is no cure although God, the Great Physician, could do so, but as long as we mortals inhabit this earth there will be sickness and sorrow.  And who am I to think that I deserve to escape what so many of my fellow humans are presently coping with?  The prayer of Serenity is so appropriate.   And I’m certain that many of us pray that over and over again because there are certainly things we cannot change, and we need His strength to endure what we cannot change and the wisdom to know the difference. That not only goes for those of us with cancer but it applies to other problems in life.

So Cathy, it’s good to know that this cancer was discovered in the “early stage”.  And if you’re concerned about the long interval of time in between checkups, why not ask the doctor to schedule your appointments every 3 months instead.  A tumor marker can rise significantly over a 6-month period.  And it seems to me that a PET/CT or a CT scan should be done at least yearly.  My husband is now entering his 15^th year of survival from Esophageal Cancer Stage III.  He is followed up by our oncologist every 6 months and has a yearly PET scan.  My oncologist schedules a PET or CT scan depending on my needs not on a calendar basis.  He doesn’t operate by the clock, and gives me all the time I need.  Five minutes would not be an ample consultation, and I would leave with a lot of unanswered questions if that’s all the time he spent with me.  If I happen to have any kind of unusual problem between visits, I have his nurse’s number.  I call her—she talks with my oncologist—and they schedule an impromptu visit if they think it necessary.  You deserve that kind of relationship with your medical team. 

Lastly, Cathy, I’ve found lots of articles that indicate that Ovarian cancer patients can also possess the overactive gene that has more receptors and over-expresses itself more rapidly in those patients who have it, as opposed to those who do not have it.  I know some patients on the Esophageal site have taken this Herceptin as a maintenance drug.  Herceptin (Trastuzumab ) is not a chemotherapy drug but is highly effective in the treatment of that over-expressive gene that makes the cancer spread more quickly.

There are lots of references below, and I confess to having only a vague understanding of the technical jargon, but I think that there is helpful information for you.  I would think that you should be monitored on a fairly regular schedule.  Personally, I think you’re worth more than 5-minutes of the doctor’s time. 

Wishing you all the best,

Loretta

Peritoneal Carcinomatosis/Ovarian Cancer Stage IV

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1.        http://www.herceptin.com/about?cid=her_PS_MBHRUA7022_1&c=MBHRUA7022

“About Herceptin

2.        http://news.cancerconnect.com/types-of-cancer/

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3.        http://news.cancerconnect.com/types-of-cancer/ovarian-cancer/stage-i-ovarian-cancer/

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4.        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745605/

5.        https://www.ncbi.nlm.nih.gov/pubmed/16944270

Occurrence of both breast and ovarian cancer in a woman is a marker for the BRCA gene mutations: a population-based study from western Sweden…

Abstract - AIM: This study aimed to analyze whether the occurrence of both breast and ovarian cancer in a woman serves as a marker for BRCA gene mutations.

MATERIAL AND METHODS:

This population-based study included 256 women in western Sweden who developed both invasive breast and ovarian tumors between 1958 and 1999. Archival paraffin tissue blocks of their tumors were retrieved for DNA-extraction to analyze the founder mutation, BRCA1 c.3171_3175dup (c.3171ins5), which is most common in this geographic area and four other common Scandinavian BRCA1 gene mutations and one BRCA2 mutation. Together, account these mutations for approximately 75% of the BRCA1/2 gene mutations in the clinical unit.

RESULTS:

Nineteen percent (95% confidence interval (CI) 14-24%) of the women carried one of the analyzed BRCA1 gene mutations but none of the women were positive for the analyzed BRCA2 mutation. One-third of the women with both tumors before age 60 were mutation carriers. BRCA1 c.3171_3175dup (c.3171ins5) constituted 84% of all identified mutations. Although the majority of breast cancers were invasive ductal and atypical medullary types, a variety of other breast malignancies were seen among mutation carriers. Serous ovarian carcinomas predominated among ovarian tumors. A variety of other ovarian tumors, including three granulosa-theca cell tumors, were also observed among mutation carriers.

CONCLUSIONS:

6.        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042515/

HER2 Status in Ovarian Carcinomas: A Multicenter GINECO Study of 320 Patients…

Background

Despite a typically good response to first-line combination chemotherapy, the prognosis for patients with advanced ovarian cancer remains poor because of acquired chemo resistance. The use of targeted therapies such as trastuzumab may potentially improve outcomes for patients with ovarian cancer.

 HER2overexpression/amplification has been reported in ovarian cancer, but the exact percentage of HER2-positive tumors varies widely in the literature.

In this study, HER2 gene status was evaluated in a large, multicentric series of 320 patients with advanced ovarian cancer, including 243 patients enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin-based chemotherapy.

Methodology/Principal Findings

The HER2 status of primary tumors and metastases was evaluated by both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis of paraffin-embedded tissue on conventional slides.

The prognostic impact of HER2 expression was analyzed. HER2 gene was overexpressed and amplified in 6.6% of analyzed tumors. Despite frequent intratumoral heterogeneity, no statistically significant difference was detected between primary tumors and corresponding metastases.

Conclusions/Significance

Our results show that the decision algorithm usually used in breast cancer (IHC as a screening test, with equivocal results confirmed by FISH) is appropriate in ovarian cancer.

7.        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861058/

Trastuzumab Sensitizes Ovarian Cancer Cells to EGFR-targeted Therapeutics

Background

“Early studies have demonstrated comparable levels of HER2/ErbB2 expression in both breast and ovarian cancer. Trastuzumab (Herceptin), a therapeutic monoclonal antibody directed against HER2, is FDA-approved for the treatment of both early and late stage breast cancer. However, clinical studies of trastuzumab in epithelial ovarian cancer (EOC) patients have not met the same level of success. Surprisingly, however, no reports have examined either the basis for primary trastuzumab resistance in ovarian cancer or potential ways of salvaging trastuzumab as a potential ovarian cancer therapeutic…

Results

In contrast to widely held assumptions, here we show that ovarian cancer cells that are not growth inhibited by trastuzumab are still responsive to trastuzumab. Specifically, we show that responsiveness to alternative HER-targeted inhibitors, such as gefitinib and cetuximab, is dramatically potentiated by long-term trastuzumab treatment of ovarian cancer cells. HER2-positive ovarian carcinoma-derived cells are, therefore, not "unresponsive" to trastuzumab as previously assumed, even when they not growth inhibited by this drug.

Conclusions

Given the recent success of EGFR-targeted therapeutics for the treatment of other solid tumors, and the well-established safety profile of trastuzumab, results presented here provide a rationale for re-evaluation of trastuzumab as an experimental ovarian cancer therapeutic, either in concert with, or perhaps as a "primer" for EGFR-targeted therapeutics…”

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8.        https://www.biooncology.com/pathways/cancer-tumor-targets/her-pathways.html

9.        http://mlabs.umich.edu/files/pdfs/BRCA_FAQ.pdf

 “…Does MMGL provide detailed interpretations of test results?

Yes, MMGL provides a comprehensive interpretation of BRCA1 and BRCA2 variants using a thorough review of medical literature sources and currently available bioinformatics tools and databases. The following are examples of interpretation we use for the different types of variants.  In some cases, MMGL will provide more background for interpretation in unique variant circumstances.

 • Pathogenic variant: indicates a higher risk for BRCA1/BRCA2 related cancers.

However, it is important to note that not all individuals with pathogenic BRCA1 or BRCA2 variants will have breast or ovarian cancer.

 Women with BRCA1 or BRCA2 pathogenic variants face an estimated 40-80% lifetime risk for breast cancer and 11-40% for ovarian cancer.

In addition men with BRCA1 or BRCA2 pathogenic variants face an estimated 1-10% lifetime risk for breast cancer (Ford et al. Am J Hum Genet 62:676-689, 1998; Antoniou et al. J Med Genet 42:602-603, 2002; Antoniou et al. Am J Hum Genet 72:1117-1130, 2003; http://www.ncbi.nlm.nih.gov/books/NBK1247/).

Other types of cancers have also been reported in individuals with pathogenic BRCA1 and BRCA2 variants (http://www.ncbi.nlm.nih.gov/books/NBK1247/).

 • Variant of uncertain clinical significance (VUS): indicates that the risk for BRCA1/BRCA2 related cancers cannot be determined based on this result. The result should be evaluated in conjunction with other clinical information, diagnostic findings and family history. Clinical targeted testing (single site BRCA analysis) of the VUS in other affected and unaffected family members may help clarify the clinical significance of this variant. Medical Genetics evaluation and counseling is strongly recommended.

 • No pathogenic variants: indicates that variants associated with a higher risk for BRCA1/BRCA2 related cancers were not observed. This result should be evaluated in conjunction with other clinical information, diagnostic findings and family history. For patients without a personal history of cancer who have a family history of breast and/or ovarian cancer, testing of an affected family member should be considered. Medical Genetics evaluation and counseling is strongly recommended…”

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12.    http://www.ovcare.ca/about_ovarian_cancer/types_of_ovarian_cancer/

Epithelial origin - High-Grade Serous Carcinoma

High-grade serous carcinoma is the most malignant form of ovarian cancer and accounts for up to 70% of all ovarian cancer cases. The majority of high-grade serous ovarian cancers have recently been found to originate in the fallopian tube, not the ovary…”

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13.    http://www.ovcare.ca/about_ovarian_cancer/faqs/

“Frequently Asked Questions…

“…Q: What are the survival rates for women diagnosed with ovarian cancer?
A: Most cases of high grade serous ovarian cancer are diagnosed at an advanced stage (stage 3 or 4) and the disease is widespread. In these cases, the 5 year survival rates are 15 per cent.

For those diagnosed early in stage 1 or 2, the five year survival rate is much higher at approximately 80 per cent…

Q: Isn’t ovarian cancer one disease?
A: Ovarian cancer is now known to have a number of subtypes, which originate in different areas, develop in different ways, and respond differently to treatment. Some of the commonly known ovarian cancer subtypes are: high-grade serous cancer, clear cell carcinoma, and endometrioid cancer…”

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