CAPITULO I: MARCO CONCEPTUAL
5. ANTECEDENTES BIBLIOGRÁFICOS
With the increase in knowledge of hereditary breast cancer risk the relative mer- its (or otherwise) of different options (surveillance or prophylactic intervention) available for women referred to the cancer family clinic ought to become clearer but, in fact, the necessary evidence is proving difficult to compile. The following questions are relevant, though answers are currently far from complete:
1. How do women in Scotland react to discussions of prophylactic oophor- ectomy and/or prophylactic mastectomy?
2. What is the take-up rate for surgery and at what age?
3. Is uptake of prophylactic surgery related to objective estimate of risk or to family responsibilities (young children, etc) or to other identifiable factors such as social class?
4. On follow up, are women satisfied with the results of the surgery and, (if possible) how content with their decision are women who opt not to proceed to surgery?
Cost/ benefit issues in relation to prophylactic surgery or screening are covered in Chapter 7.
As discussed in Chapter 2, bilateral prophylactic mastectomy has been shown to be highly effective in providing long-term protection against breast cancer for women at very high genetic risk. Before the BRCA genes were discovered, a few women with very striking family histories opted for this procedure, even though their own risk of carrying the (then unknown) causal mutation could not have been greater than 50%.
In such a setting, it could be argued that the surgery was treating anxiety as much as preventing cancer. However, anxiety can be very debilitating and, given the family situation, the decision to proceed with total removal of the breasts is defensible.
In recent years, the technical aspects of total mastectomy and reconstruction have advanced considerably and greater numbers of women at high risk are now in a position to know their own genetic status. Furthermore, the findings of the European Collaborative Group set out earlier in this chapter indicate that, for BRCA1 mutation-carriers, annual surveillance alone provides inadequate pro- tection.
In my experience, patients at high risk are willing to consider prophylactic sur- gery, yet the uptake is still very low. There is almost certainly a “cultural” com- ponent in this decision and therefore clinicians must consider the women’s val- ues and cultural background as well as her personal preferences when discuss- ing with them the issues of prophylactic risk reducing interventions.
Issues arise in relation to the long-term impact of breast removal on women’s sexuality and psychosocial consequences both of the surgery and of their muta- tion carrier status.
In the McLeish study (2003),189the proportion of women from the Tayside clinic opting for prophylactic surgery was small in comparison to other centres in Eng- land and other European countries. There appeared to be unrealistic expecta- tions of mammography and little perception of the relative value of prophylactic surgery among the risk-reducing measures currently available.
McLeish also found that a third of the women in the survey considered prophy- lactic surgery to be “not really acceptable” or “unacceptable”. These findings were similar to those of Meijers-Heijboer et al. (2000)208in the Netherlands. This makes the demand for prophylactic breast surgery considerably weaker than for mammography. McLeish also found that attitudes to prophylactic ovarian risk-reducing surgery were guarded, though more favourable than towards pro- phylactic mastectomies.
In France, Eisinger et al. (2000)209 reported that only 4.7% of the women in their study found it acceptable to consider surgical intervention as a cancer risk- reducing measure in young women. When a causal BRCA mutation has been demonstrated, however, attitudes to surgery may change and the Dutch group led by Meijers-Heijboer (2000)208 found that as many as 51% of such women would opt for prophylactic surgical intervention.
No form of prophylactic surgery should be treated lightly and total mastectomy with reconstruction of the breast is a major procedure. It is therefore import- ant to alert women to the real risks of such interventions before they are asked to take a decision. For example, there can be surgical complications, varying from haematomas or infection to failure of reconstruction, requiring removal of implants or reconstructed breast tissue (in the case of reconstruction failure). Even in the technically simpler case of oophorectomy, complications can include infection, bleeding, urinary and/or bowel injuries and, of course, premature menopause which may require a period of hormone replacement therapy. All of these possible complications (together with the natural reluctance to go “under the knife”) no doubt contribute to the limited uptake of risk-reducing surgery.
To date, I have not detected much shift in attitudes but the disappointing out- come of regular screening for BRCA1 mutation-carriers has not yet been publi- cised and is only beginning to be disseminated through the clinic, so attitudes towards surgical intervention to reduce cancer risk may change. Furthermore, with the prospect that the NICE guidelines on inherited breast cancer may be ad- opted widely across the UK (including Scotland), the proportion of “high risk” women eligible for genetic testing will be higher than at present (under SIGN guidelines).
This may contribute to an increase in numbers of known mutation carriers. Overall, therefore, I expect demand for prophylactic surgical interventions to increase substantially in the future (as discussed above).
Since the study commenced, two women found to carry the same (BRCA2) mutation as an affected relative, have discussed prophylactic bilateral mastec- tomies. Only one has undergone the procedure to date. I ought to highlight that the number of women being considered for bilateral prophylactic mastectomy has increased gradually over the past decade. However, the number of women who decided to go ahead with surgery remains very low.
While the foregoing refers to prophylactic mastectomies in women who are aware of their “high risk” status but are disease-free, there is a second category of women for whom preventive mastectomy is considered, namely “high risk” women who have already been diagnosed with unilateral breast cancer, have had their primary cancer treatment but seek advice on risk-reducing surgery for the contra-lateral (unaffected) breast. This would also include those who, some time after their breast cancer treatment, were found to carry a mutation in one of the BRCA genes.
It is understandable that patients, who have already experienced cancer, may be less reluctant to contemplate the drastic measure of complete breast tissue re- moval. Most of them are satisfied with their decision to undergo the procedure. A study by Geiger and colleagues210 has demonstrated contentment with the decision to have prophylactic contra-lateral surgery in 86.5% of their cohort (n=371) and also reported contentment with subsequent quality of life (compar- able to that of breast cancer survivors who had declined risk reducing surgery). However, their study results applied to a wide range of women with breast can- cer diagnosis and because the study had little information on patients with fam-
ily histories of breast cancer, the results may not apply specifically to “high risk” breast cancer women.
Since 1994, eleven patients from the Tayside breast cancer family history clinic were treated for breast cancer and subsequently have had prophylactic contra- lateral breast surgery. In two of these, an unsuspected carcinoma was found on pathological examination of the removed tissue. Neither was an invasive malignancy (they were DCIS) and both patients remain on regular follow up. One has a BRCA1 mutation and the other BRCA2. One other patient who had contra-lateral prophylactic surgery has since died from metastatic breast cancer. She was a BRCA1 mutation carrier.
Of those eleven patients with previous breast cancer and who underwent contra- lateral prophylactic mastectomy, four were known to carry a mutation; one of them in fact had mutations in both BRCA1 and 2 genes.
Although data were not formally collected, in informal conversations with those individuals it emerged that the major factors influencing their decision to un- dergo the procedure were: a) molecular confirmation of their high risk status and b) perceived needs of their family—particularly their commitments to the raising of children.
The mean age for undertaking bilateral prophylactic mastectomy in women who had previous breast cancer diagnosis was 45 years (range: 34–59) and, for those undergoing prophylactic mastectomy only because of their high risk status (no previous breast cancer), it was 44 years (range: 36–56; there was no significant difference between the two groups).