Premenopausal stage 1 ovarian suppression/oophorectomy?

Salamandra

My understanding is that ER+ is more likely to recur long term, and that ovarian suppression with AI or oophorectomy seems to be more effective than tamoxifen for preventing distant recurrence.

Is it overkill for stage 1? Has anyone been offered or recommended this by their doctor? I have family history but no known genetic mutations.

I'm 39, no kids and okay with not having kids. Tamoxifen seems to have enough side effects in common with menopause... or won't I know until I've tried it?

Spoonie77

Hi Salamandra - My MO suggested I try Tamo before looking at Ovarian Suppression/Surgery. I'm still looking at my my bottle of Tamoxifen. I haven't decided what I want to do yet as far as that goes. It's pretty scary to me, given the balance my QOL was in prior to BC. I also do not have any genetic mutations, but do have family history as well, mostly on my paternal side.

I can tell you I'm very interested in hearing more about what you mentioned, that suppression/surgery is perhaps more effective than Tamox on preventing dist recur. Hopefully others will chime in. If not, I'm putting that on the list to ask my MO when I see her in a few weeks. In the meantime, it's on my "To Google" list. LOL.

I do kind of get the feeling from most people that with everyone being so different, not one of us will really know how we will react to the Tamox until we try it. But man, there are some heavy risks and some permanent ones that come along with that. Not something I'm willing to throw into my mix lightly. Needs lots of deliberation.

Kudos to you for asking questions and wanting to do whats best for you.

Careninnj

my stats are below. But im brca2+. So im actually having my tubes and ovaries removed in 2 weeks.

Salamandra

So far I have a lot more 'research' collected on radiation than on endocrine therapy. But this seems to be a pretty good summary of AI + OS for premenopausal at this point. I'm adding it to my document.

Like so much breast cancer stuff: needs more research/pick your poison/depends on individual factors!

Aromatase inhibitors in premenopausal women with breast cancer: the state of the art and future prospectshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC59277...------

The abcsg (Austrian Breast and Colorectal Cancer Study Group)–12 trial has shown a comparable dfs for 3-year adjuvant therapy with anastrozole–goserelin and tamoxifen–goserelin38. However, the recent results of the soft and text trials provided additional evidence about ais as adjuvant treatment in premenopausal bca patients. A combined analysis of the data from those two trials demonstrated that, compared with tamoxifen plus ovarian suppression, adjuvant endocrine therapy with exemestane plus ovarian suppression in premenopausal patients with hr+ bca was associated with a significantly improved dfs and an extended disease-free interval and interval without distant recurrence.

The differing results emerging from abcsg-12 and the text and soft trials might be related to higher statistical power in the latter combined analysis (with 3 times the number of events) and varying treatment durations: the 3-year duration of ai therapy in abcsg-12 might have been insufficient compared with 3 years of tamoxifen because the study manifested a carryover effect after treatment interruption.

Given the foregoing evidence, adjuvant treatment with ovarian suppression plus exemestane represents an important option, especially for very young women (<35 years of age) who have sufficient risk of recurrence to suggest adjuvant chemotherapy. However, follow-up in text and soft is relatively short, and few data about long-term adverse events are available.

The choice of endocrine treatment should be based on patient comorbidities and the toxicity profiles of the various drugs: tamoxifen is associated with menopausal symptoms (hot flashes, sweats, weight gain, and sexual dysfunction), thromboembolic events, endometrial hyperplasia, and uterine tumours. Compared with tamoxifen plus ovarian suppression, exemestane plus ovarian suppression is associated with more frequent adverse sexual, musculoskeletal, and bone density events.

...

No specific endocrine resistance mechanisms have been identified in young women, and all therapeutic strategies developed to reverse endocrine resistance have, until now, been applied only in postmenopausal patients.

Overweight represents a potential factor in endocrine resistance to hormonal therapy with ais. The hr+ form of bca often occurs in overweight women, and recent data demonstrate a negative effect of body mass index (bmi) on ai efficacy in postmenopausal women42. In particular, the atac study randomized 5172 postmenopausal women with early hr+ bca to receive hormonal therapy with tamoxifen or the aianastrozole. The study demonstrated a higher risk of local recurrence and metastasis in patients with a bmiexceeding 35, and treatment with anastrozole was associated with a higher risk of recurrence in women with a bmi exceeding 30. In contrast, the efficacy of tamoxifen was independent of bmi43. Whether, compared with their normal-weight counterparts, overweight premenopausal women receiving adjuvant ais can experience the same benefit for reduced risk of recurrence is currently unclear. The data from abcsg-12 seem to agree with those emerging from the atac study. The latter trial investigated the effect of bmi on the efficacy of endocrine therapy in the adjuvant setting in premenopausal women. Compared with women receiving tamoxifen, women with a bmi of 25 kg/m2 or greater, treated with anastrozole, had a 50% higher risk of disease recurrence (95% ci: 0.93 to 2.38; p = 0.08) and a risk of death that was increased by a factor of 3 (95% ci: 1.35 to 6.82; p = 0.004)44.

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FarAwayToo

Salamandra, take a look at SOFT and TEXT clinical trials - they are the one that concluded that OS +AI was more effective in preventing recurrences, HOWEVER, the big side note is that the difference were only seen in high risk women, those who had high enough risk to be recommended chemotherapy.

Did you have Oncotype DX or Mammaprint done on your tumor? If yes, were you high risk? If not, the additional benefit from ovarian suppression may not be significant for you. I suggest discussing this in length with your oncologist, and I would ask them to show you statistics that applies to your risk group.

I am high risk based on Mammaprint, and my oncologist suggested ovarian suppression an AI based on the results of TEXT and SOFT. I had ovarian failure from chemo, then went on Lupron right after chemo to keep my ovaries asleep. Started letrozole (AI) 2 months later. After several months I decided to remove my ovaries so that I didn't have to do Lupron shots every month. I also didn't want to worry about effectiveness of ovarian suppression from Lupron.

Whatever you decide, I suggest you do reversible measures first. I know I was scared and wanted to prevent recurrence no matter what (I still do). But overtreatment is not good either. Instant menopause is no picnic. Mine wasn't really instant as I started having menopausal symptoms during chemo, when my ovaries stopped working. Symptoms didn't worsen too much with Lupron, but I started feeling more effects of estrogen deprivation when I started taking AI. If Tamoxifen is effective for you, you'll notice some of the symptoms too. The biggest blow was after I had my ovaries out. Or maybe it was a compound effect of taking AIs for 6 months by then. I'm just now adjusting to my new normal.

Tresjoli2

my ob/gyn refused to remove my ovaries. Said they provide other important benefits and he did not recommend their removal.

Salamandra

Thank you FarAwayToo and Tresjoli2. I really appreciate hearing your experiences!

Spoonie77

Salamandra - Found this article tonight while whiling away the hours of insomnia. Maybe this may be helpful for your decision process?

It cleared up some things for me as to why my MO suggested that we try all hormonal options first, and as a last resort, look at surgical options.

published 2016

Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression Summary

http://ascopubs.org/doi/full/10.1200/jop.2016.0112...

"Recommendations

• 1. Should premenopausal women with ER-positive tumors receive adjuvant ovarian suppression in addition to standard adjuvant therapy and, if so, in which subsets of patients?
  • 1.1 The Panel recommends that higher-risk patients should receive ovarian suppression in addition to adjuvant endocrine therapy and lower-risk patients should not.

Qualifying Statement:

The Panel notes that two prospective studies did not show overall clinical benefit for the addition of ovarian suppression to tamoxifen in premenopausal, ER-positive breast cancer. However, in a large subset of women with higher-risk cancers, nearly all of whom received chemotherapy but remained premenopausal, ovarian suppression added to tamoxifen reduced the risk of breast cancer recurrence. Because of the design of the clinical trials, there are few definitive criteria by which to define risk.

• 1.2 Women with stage II or stage III breast cancers who would ordinarily be advised to receive adjuvant chemotherapy should receive ovarian suppression in addition to endocrine therapy.

• 1.3 Women with stage I or II breast cancers at higher risk of recurrence, who might consider chemotherapy, may also be offered ovarian suppression in addition to endocrine therapy.

• 1.4 Women with stage I breast cancers not warranting chemotherapy should receive endocrine therapy but should not receive ovarian suppression.

• 1.5 Women with node-negative cancers ≤ 1 cm (T1a, T1b) should receive endocrine therapy but should not receive ovarian suppression.

[Benefits: increasing disease-free survival (DFS), freedom from breast cancer, and freedom from distance recurrence. Harms: worse menopausal symptoms and sexual functioning, including hot flashes, sweating, weight gain, vaginal dryness, and decreased libido.]"

Spoonie77

Also there is this article as well...

Adjuvant Ovarian Suppression in Premenopausal Breast Cancer

https://www.nejm.org/doi/full/10.1056/NEJMoa1412379

"

RESULTS

After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen–ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen–ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane–ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).

CONCLUSIONS

Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression. (Funded by Pfizer and others; SOFT ClinicalTrials.gov number, NCT00066690.)

"

Salamandra

Thank you Spoonie! So much hanging on this oncotye thing!

I think one confusing thing is that the numbers in that second study, 84.7% vs 86.6%... that's a pretty equivalent or even greater benefit than the difference in any individual study comparing long term cancer benefits of radiation versus no radiation. But medical standard of practice comes down 100% for radiation after lumpectomy. Partly because over many studies, they decided in the aggregate that it's actually statistically significant.

Well, more questions for the docs tomorrow... so glad to finally be meeting them!

Spoonie77

Good luck with your appt tomorrow! Hope they have the answers you need.

Salamandra

Thank you Spoonie!

I liked the medical oncologist a lot. She seemed fairly conservative in terms of treatment orientation, but she was open to me going the luprone/AI course if I wanted so I wouldn't have to go off my antidepressant that's been working for so long. But she was also able to explain in a way that made sense to me why she didn't think, for my particular tumor/situation, it would have any clinical superiority over tamoxifen apart from letting me stay on that drug.

So plan A is the tamoxifen, and hopefully all will go well.