Douching, Talc Use, and Risk of Ovarian Cancer

Are women who douche almost twice as likely to get ovarian cancer?

A douche flushes water up into the vagina and clears out natural secretions designed to keep the vagina healthy, which may increase the risk of infections.

There are concerns some douching products could introduce phthalates – chemicals that may disrupt hormone regulation – into the reproductive tract, which could increase the risk of ovarian cancer.

Concerns have also been raised that genital talc, often used in combination with douching, may increase cancer risk.

Abstract

Background
Douching was recently reported to be associated with elevated levels of urinary metabolites of endocrine disrupting phthalates, but there is no literature on douching in relation to ovarian cancer. Numerous case-control studies of genital talc use have reported an increased risk of ovarian cancer, but prospective cohort studies have not uniformly confirmed this association. Behavioral correlation between talc use and douching could produce confounding.

Douching, Talc Use, and Risk of Ovarian Cancer, Epidemiology, June 20, 2016.

Methods
The Sister Study (2003-2009) enrolled and followed 50,884 women in the US and Puerto Rico who had a sister diagnosed with breast cancer. At baseline participants were asked about douching and talc use during the previous 12 months. During follow-up (median of 6.6 years) 154 participants reported a diagnosis of ovarian cancer. We computed adjusted hazard ratios (HR) and 95% confidence intervals (CI) for ovarian cancer risk using the Cox proportional hazards model.

Vaginal douching ‘linked to increased ovarian cancer risk’, nhs choices, August 4 2016.

Results
There was little association between baseline perineal talc use and subsequent ovarian cancer (HR: 0.73 CI: 0.44, 1.2). Douching was more common among talc users (OR: 2.1 CI: 2.0, 2.3), and douching at baseline was associated with increased subsequent risk of ovarian cancer (HR: 1.8 CI: 1.2, 2.8).

Conclusions
Douching but not talc use was associated with increased risk of ovarian cancer in the Sister Study.

Clear Cell Adenocarcinoma of the Ovary Associated with In Utero DES Exposure

A 45-year-old white woman was referred to an outpatient clinic with a self-discovered lump in the left lower abdominal quadrant

Abstract

Background
To our knowledge, this patient is the first clinical case featuring clear cell adenocarcinoma of the ovary that may be linked to diethylstilbestrol exposure in utero. We would like to emphasize that clear cell adenocarcinoma of the vagina and cervix, not the ovary, were previously shown to be sites for tumors in female offspring exposed prenatally to DES.

Case
A 45-year-old woman presented with a self-discovered lump in the lower abdominal quadrant. She underwent surgery and staging that revealed clear cell adenocarcinoma confined to the left ovary. Foci of high-grade squamous neoplastic proliferation, inflammation, and a paratubal cyst were also present on the pathology specimen. Medical records established unequivocally that the patient’s mother received diethylstilbestrol therapy throughout the pregnancy. since clear cell cancers can develop, not infrequently, in foci of endometriosis, our patient’s pathology specimen was carefully inspected for endometriosis and none was found. Moreover, evidence linking prenatal DES exposure with chronic ovarian inflammation, paraovarian cysts, and high-grade squamous neoplastic proliferation in the genital tract has been accumulating. Although our patient is older than most patients in the Herbst cohort and a sporadic case of clear cell carcinoma cannot be excluded with certainty, all of the above changes were present in our patient’s pathology specimen. This further enhances our degree of suspicion on the causality between in utero DES exposure and the clear cell adenocarcinoma of the ovary in our patient.

Clear Cell Adenocarcinoma of the Ovary Associated With In Utero Diethylstilbestrol Exposure: Case Report and Clinical Overview, Medscape J Medv.11(1); 2009PMC2654676, 2009 Jan 7.

Conclusion
Our case is consistent with clear cell adenocarcinoma, probably related to diethylstilbestrol exposure in utero. Our case of probable DES-induced transplacental carcinogenesis more than 4 four decades after exposure reinforces the need for continued vigilance and routine gynecologic examinations in individuals prenatally exposed to this drug.

More DES DiEthylStilbestrol Resources

Ovary Removal tied to Colon Cancer Risk

Hysterectomy and health risks: if given a choice, keep your ovaries

Ovary Removal Tied to Colon Cancer Risk, NY Times, MAY 4, 2016

Removal of the ovaries — a procedure known as oophorectomy — may increase the risk for colorectal cancer, a new study concludes.

Abstract

Population‐based analysis of colorectal cancer risk after oophorectomy, bjs, Apr 26, 2016.

Background
The development of colorectal cancer is influenced by hormonal factors. Oophorectomy alters endogenous levels of sex hormones, but the effect on colorectal cancer risk is unclear. The aim of this cohort study was to examine colorectal cancer risk after oophorectomy for benign indications.

Methods
Women who had undergone oophorectomy between 1965 and 2011 were identified from the Swedish Patient Registry. Standard incidence ratios (SIRs) and 95 per cent confidence intervals for colorectal cancer risk were calculated compared with those in the general population. Stratification was carried out for unilateral and bilateral oophorectomy, and hysterectomy without specification of whether the ovaries were removed or not. Associations between the three oophorectomy options and colorectal cancer risk in different locations were assessed by means of hazard ratios (HRs) and 95 per cent confidence intervals calculated by Cox proportional hazards regression modelling.

Results
Of 195 973 women who had undergone oophorectomy, 3150 (1·6 per cent) were diagnosed with colorectal cancer at a later date (median follow‐up 18 years). Colorectal cancer risk was increased after oophorectomy compared with that in the general population (SIR 1·30, 95 per cent c.i. 1·26 to 1·35). The risk was lower for younger age at oophorectomy (15–39 years: SIR 1·10, 0·97 to 1·23; 40–49 years: SIR 1·26, 1·19 to 1·33; P for trend < 0·001). The risk was highest 1–4 years after oophorectomy (SIR 1·66, 1·51 to 1·81; P < 0·001). In the multivariable analysis, women who underwent bilateral oophorectomy had a higher risk of rectal cancer than those who had only unilateral oophorectomy (HR 2·28, 95 per cent c.i. 1·33 to 3·91).

Conclusion
Colorectal cancer risk is increased after oophorectomy for benign indications.

Promising new screening test for ovarian cancer needs more study

It may soon be possible to screen for ovarian cancer

image of woman-and-sky
There is no reliable way to detect ovarian cancer, which may explain why most women who are diagnosed already have advanced disease. But a new test may change that. Look II.
2015 Study Summary

The exciting thing about this paper is that it’s the first evidence that suggests if you catch the cancer early enough, perhaps it can save lives

Background
Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality.

Methods
In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032.

Findings
Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS, 50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0–14 of 15% (95% CI −3 to 30; p=0·10) with MMS and 11% (−7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (−20 to 31) in years 0–7 and 23% (1–46) in years 7–14, and in the USS group, of 2% (−27 to 26) in years 0–7 and 21% (−2 to 42) in years 7–14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (−2 to 40) and a reduction of 8% (−27 to 43) in years 0–7 and 28% (−3 to 49) in years 7–14 in favour of MMS.

Interpretation
Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7–14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening.

Sources and more information
  • Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial, The Lancet, doi.org/10.1016/S0140-6736(15)01224-6, 17 December 2015.
  • Early Detection of Ovarian Cancer May Become Possible, NY Times, DEC. 17, 2015.
  • It May Soon Be Possible to Screen for Ovarian Cancer, time, Dec. 17, 2015.

Recurrent ovarian cancer: gene therapy may improve patients survival

AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer

ovarian-cancer image
Use of gene therapy to deliver a protein that suppresses the development of female reproductive organs may improve the survival of patients with ovarian cancer that has recurred after chemotherapy, which happens 70 percent of the time and is invariably fatal. Ovarian cancer image via MedicalXpress

2015 Study Abstract

To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. We have recently engineered peptide modifications to human MIS [albumin leader Q425R MIS (LRMIS)] that increase production and potency in vitro and in vivo. To test this novel therapeutic peptide, serous malignant ascites from highly resistant recurrent ovarian cancer patients were isolated and amplified to create low-passage primary cell lines. Purified recombinant LRMIS protein successfully inhibited the growth of cancer spheroids in vitro in a panel of primary cell lines in four of six patients tested. Adeno-associated virus (AAV) -delivered gene therapy has undergone a clinical resurgence with a good safety profile and sustained gene expression. Therefore, AAV9 was used as a single i.p. injection to deliver LRMIS to test its efficacy in inhibiting growth of palpable tumors in patient-derived ovarian cancer xenografts from ascites (PDXa). AAV9-LRMIS monotherapy resulted in elevated and sustained blood concentrations of MIS, which significantly inhibited the growth of three of five lethal chemoresistant serous adenocarcinoma PDXa models without signs of measurable or overt toxicity. Finally, we tested the frequency of MIS type II receptor expression in a tissue microarray of serous ovarian tumors by immunohistochemistry and found that 88% of patients bear tumors that express the receptor. Taken together, these preclinical data suggest that AAV9-LRMIS provides a potentially well-tolerated and effective treatment strategy poised for testing in patients with chemoresistant serous ovarian cancer.

Sources and more information
  • AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer, PNAS, doi: 10.1073/pnas.1510604112, July 27, 2015.
  • Gene therapy may improve survival of patients with recurrent ovarian cancer, MedicalXpress, July 27, 2015.

UKCTOCS new screening technique might pick up twice as many women with ovarian cancer

Risk Algorithm Using Serial Biomarker Measurements for Ovarian Cancer Screening

ukctocs-team
The aim of the trial is to see if either of these tests can help doctors diagnose women with ovarian cancer when their cancer is at an early stage. If the tests work well enough it could mean that women with ovarian cancer may be diagnosed earlier, and their cancer treated more effectively. UKCTOCS team image.

2015 Study Abstract

Purpose
Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates.

Patients and Methods
In the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves.

Results
After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869).

Conclusion
Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded.

Sources and more information
  • U.K. Familial Ovarian Cancer Screening Study (UK FOCSS), Phase 2 Patient Information Sheet, Version 9, August 09.
  • Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening, Journal of Clinical Oncology, doi: 10.1200/JCO.2014.59.4945, June 20, 2015.
  • New screening technique could pick up twice as many women with ovarian cancer, eveappeal, UKCTOCS screening results.

Live birth after transplantation using ovarian tissue from childhood

Live birth after autograft of ovarian tissue cryopreserved during childhood

childhood-memories
In a world first, a woman with ovarian failure has successfully given birth to a healthy baby after receiving transplantation of ovarian tissue from her childhood. Memories of Childhood image by Amy Dianna.

A patient whose right ovary was removed as a teenager, and whose left ovary subsequently failed, has become the first woman in the world to give live birth after doctors transplanted ovarian tissue that had been frozen in her youth. Medical professionals are calling this success an “important breakthrough” in fertility treatment.

2015 Study Abstract

Ovarian insufficiency is a major long-term adverse event, following the administration of a myeloablative conditioning regimen, and occurring in >80% of children and adolescents receiving such treatment for malignant or non-malignant disease. Cryopreservation of ovarian tissue is currently offered to preserve the fertility of these young patients. At least 35 live births have been reported after transplantation of cryopreserved ovarian tissue in adult patients, but the procedure remains unproven for ovarian tissue harvested at a prepubertal or pubertal age.

We report here the first live birth after autograft of cryopreserved ovarian tissue in a woman with primary ovarian failure after a myeloablative conditioning regimen as part of a hematopoietic stem cell transplantation performed for homozygous sickle-cell anemia at age 14 years. This first report of successful fertility restoration after the graft of ovarian tissue cryopreserved before menarche offers reassuring evidence for the feasibility of the procedure when performed during childhood.

Sources and more information
  • Live birth after autograft of ovarian tissue cryopreserved during childhood, Oxford Journals Medicine & Health Human Reproduction, doi: 10.1093/humrep/dev128, June 9, 2015.
  • Woman gives birth after transplantation using ovarian tissue from childhood, by Marie Ellis for Medical News Today, 10 June 2015.

New blood test screening technique could pick up twice as many women with ovarian cancer

New ovarian cancer blood test is promising – but screening still a way off

image of blood-test
A new screening test that tracks changing levels of a protein in the blood can detect twice as many ovarian cancers as conventional methods, research has shown.

A new screening method can detect twice as many women with ovarian cancer as conventional strategies, according to the latest results from the largest trial of its kind led by UCL.

The method uses a statistical calculation to interpret changing levels in women’s blood of a protein called CA125, which is linked to ovarian cancer. This gives a more accurate prediction of a woman’s individual risk of developing cancer, compared to the conventional screening method which uses a fixed ‘cut-off’ point for CA125. The new method detected cancer in 86% of women with invasive epithelial ovarian cancer (iEOC), whereas the conventional test used in previous trials or in clinical practice would have identified fewer than half of these women (41% or 48% respectively).

The results come from analysis of one arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), the world’s largest ovarian cancer screening trial, led by UCL and funded by the Medical Research Council, Cancer Research UK, Department of Health and The Eve Appeal. The trial involved 202,638 post-menopausal women aged 50 or over who were randomly assigned to two different annual screening strategies (multimodal screening or transvaginal ultrasound) or no test at all.

Sources and more information
  • New screening technique could pick up twice as many ovarian cancer cases, University College London, 5 May 2015.
  • New ovarian cancer blood test is promising – but screening still a way off, cancerresearchuk, May 5, 2015.
  • New ovarian cancer test twice as effective as existing methods, guardian, 4 May 2015.

HRT: short-term use of hormone replacement therapy linked to ovarian cancer risk increase

HRT increases ovarian cancer risk

HRT menopause treatment ‘doubles the risk of getting ovarian cancer’

HRT at menopause image
Women who undergo hormone replacement therapy (HRT) have a ‘significantly increased’ risk of developing ovarian cancer, according to a major new study.

Researchers from the University of Oxford analysed 52 previous studies involving 21,000 women found that even those who took it for less than five years raised the risk level, although it reduces once they had stopped.

The study, published in the Lancet medical journal, has led to calls for medical guidance on HRT to be updated given the “causal relationship” and the Medical and Healthcare Products Regulatory Authority (MHRA) said it would look at the findings.

The researchers said: ‘The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for five years from around age 50 have about one extra ovarian cancer per 1,000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1,700 users.

‘The findings that ovarian cancer risk is greatest in current users of hormone therapy, falls after use ceases, and varies by tumour type, strongly suggest a causal relationship – ie: that among otherwise similar women, use of hormone therapy increases the probability of developing the two most common types of ovarian cancer, and hence ovarian cancer as a whole.

‘At present, the WHO, European, and US guidelines about hormone therapy do not mention ovarian cancer, and the UK guidelines – which are due to be revised – state only that risk may be increased with long-term use.

‘The definite risk of ovarian cancer that is observed even with less than five years of use starting at around age 50 is directly relevant to current patterns of hormone therapy use, and hence directly relevant to medical advice, personal choices, and the current efforts to revise UK and worldwide guidelines.’

Hormone replacement therapy (HRT) and the risk of ovarian cancer

MHRA logo
MHRA statement in response to the study in The Lancet on the use of HRT.by Dr Sarah Branch, deputy director of MHRA’s Vigilance and Risk Management of Medicines (VRMM) Division

” Our advice has always been that the lowest effective dose of HRT should be used for the shortest possible time.

‘We will evaluate the findings of this study and its implications for shorter term use and update product information as necessary.

‘Women on HRT should have regular health check-ups and their need to continue treatment should be reassessed at least annually. Any woman on HRT who has any questions should speak to her doctor who is best placed to advise.”

Sources and more information
  • Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies, the lancet, abstract and full study PDF, 12 February 2015.
  • Short-term use of hormone replacement therapy associated with increased ovarian cancer risk, eurekalert, 12 February 2015.
  • HRT ‘increases ovarian cancer risk‘, BBC News, 13 February 2015

Ovarian Cancer New Test to differentiate between Tumour Stages

1 in 69 women will develop ovarian cancer in her lifetime

Abstract

The BMJ
Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study.

Objectives
To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours.

Design
Observational diagnostic study using prospectively collected clinical and ultrasound data.

Setting
24 ultrasound centres in 10 countries.

Participants
Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients.

Main outcome measures
Histological classification and surgical staging of the mass.

Results
The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate.

Conclusions
The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology.

Sources and more information:

  • Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study,
    The BMJ 2014;349:g5920, 15 October 2014.
  • New test to distinguish between ovarian tumours,
    NHS Choices, October 16 2014.
  • New test ‘helps identify best ovarian cancer treatment’,
    BBC News Health, October 16 2014.