Surgical conservative treatment in breast cancer

- from desiderate to reality

I. Iordache, O. Unc, Lizica Itu, V. Sârbu

IInd General Surgery Clinic – Prof. Univ. Dr. V. Sârbu

Faculty of Medicine, Constanţa “Ovidius” University

Key words: breast cancer, conservative treatment, ‘quality of life’

Iordache Ionut
Sălciilor 102, Constanţa
Tel – 0726415037
E-mail – eduardiordache@yahoo.com
 Summary

In the last 4 decades the concept of conservative surgery imposed itself as a viable
alternative in the therapeutic scheme of breast cancer. The evolvement was determined by the
conclusions of numerous randomized clinical studies and by the special attention given to the
quality of life of the patients diagnosed with breast cancer, so that the actual standard of treatment
in breast cancer in stages Ist, and IInd is represented by conservative surgery techniques.
Although this pathology represents a constant preoccupation in the last 6 years in the
Surgery Clinic II, the number of conservative surgery in breast cancer represents only 8.14% out
of a total number of interventions for breast cancer.
The purpose of this article is to present the experience in this domain in the Surgery
Clinic II and to identify the problems of application into practice of this concept in the context
of Romanian medicine, wishing that this therapeutical option to become a reality in the surgery
of breast cancer in our country.

Résumé

Dans les dernières quatre décennies, le concept du chirurgie conservatoire a été imposé
comme une viable alternative dans le thérapeutique arsenal du cancer de sein. Cette évolution a
été déterminée par les conclusions du nombreux clinques études aussi randomisé par l’attention
remarquable accordée la qualité du vie des patientes diagnostiques avec néoplasme mammaire,
telle que le standard actuelle du traitement du cancer de sein dans le stades I et II est représenté
par les techniques du chirurgie conservatoire.
Quoique cette problématique représente une constante préoccupation du II -éme Clinique
de Chirurgie, le nombre d’interventions chirurgicales conservatoires représente seulement  un
pourcentage de 8,14% de le total d’opérations pour les néoplasmes mammaires.
Le but de cet étude est la présentation d’expérience du II -éme Clinique de Chirurgie dans
cet domaine et l’identification de problèmes levés par l’appliquer en pratique de cet concept, en
contexte du médecine roumaine, cette option thérapeutique désirer devenir une réalité de la
chirurgie du cancer de sein de notre pays.
 INTRODUCTION

This article wants to be a modest pleading in favor of conservative treatment for breast

cancer, originating from the wish of identifying and overtaking the problems raised by

application into practice of this concept in the Romanian medicine, concept which, worldwide in

the last decades imposed itself as a viable alternative becoming the actual standard for stages I

and II.

The conservative treatment of breast cancer is one of the most rigorously checked

therapy out of all medical practice, numerous arguments being brought in favor of this attitude,

which I will try to synthesize as follows.

Three factors determined the conservative therapy in breast cancer:

- understanding the biology and natural history of breast cancer

- the fall of aggressive surgical and radiological therapies, removal of internal thoracic

lymph nodes and radical radiotherapy upon the regional lymph nodes, respectively.

- the introduction on large scale of mammography, capable of identifying neoplastic

tumors in infraclinical stages and of anticipating the diagnosis of breast cancer.(6)

I. MODELS OF DEVELOPMENT FOR BREAST CANCER.

In the last 4 decades the models of dissemination for breast cancer changed radically

with better understanding of natural history of this disease.

The succession of these models is as follows:

1. Halsted model - the local disease theory

In conformity with this concept, the breast cancer was considered as a local disease with

the original point to the level of the breast. In this concept the metastases are the result of cell

disemination along the lymphatic vessels (node metastases, mainly in the ipsilateral axilla but
also parasternally , along internal mamary vessels and in mediastinum), and /or blood vessels,

giving raise to distant metastases-bone, internal organs, etc.

2. Fisher model - the theory of systemical disease

In the early 70’ies following the failure of radical surgery for healing the breast cancer,

Bernard Fisher in United States and Umberto Veronessi in Italy developped the concept of breast

cancer of a systemis malady , emphasizing the importance of hematogenic disemination of

tumoral cells. They postullated the idea that cancer diseminated through the blood system even

before detecting it with consequences determined by the biology of interraction tumor-host.

Based on this concept of ‘biologic predetermination’, they made the following predictions:

a.-the extension of local treatment won’t affect the survival;

b.-sistemical treatment, even of the aparent localized tumors could be benefic and can

offer a chance of cure.(5)

3. Harris and Hellman model - intermediary concept (spectrum)

Presently, the majority of authors, adopted an intermediary concept which combines the

first two theories. The intermediary concept takes into consideration the clinical observations

which shows that some of the breast cancers will relapse locally after a relative period of time

without determining significant distant metastases, while others will be associated with distant

metastases without local relapse. Unfortunately , none of the bioligical specific features of the

priamry tumor cannot be predictive for the future behavious, as for example if the local relapse

will be first or the doistant metastases will appear first. The intermediary concept considers local

treatment- surgical and therapeutical as important as adjuvant sistemic therapy.

4. Integrattive model

Taking into cosideration all these, a new model emmerge which tries to ellucidate the

natural history of the disease, explaining not only the fisher model of biological predeterminism

but also the clinical observations which does not completely fit into the contemporary model.
 This new model is based on the concept of sleeping/latency of the tumor, which applies

in the preclinical phase inside the breast, but also later, with micrometastases which are

diseminated in the early phase of the antural history of the disease, as soon as the primary locus

developped its vascularization.

These metastases remain inactive (dormant), until a signal- perhaps the surgical

interventiuon or any other adverse event, stimulates them to a trapid growth, the evolution being

determined by the biology of interaction body-neoplastic cells.

In the avascular stage, the malignant cells are without angiogenetic potential and have a

limitted development, till an index of 105 /106 cells.

The metastases can grow rapidly if a subgroup of these cells changes the phenotype into

an angiogenetic one and/or eliminates the angiogenetic inhibition. The model suggests that the

undisturbed metastatic development of breast cancer represents a secquential evolution from a

non/angiogenetic stage to an ongiogenetic one.

The integrative model can explain the precociuous raise of hazard for the appearance of

local and distant relapses to the operated patients, combining the natural metastatic development

of undisturbed disease (Fisher effect) with the angiogenetic signal which follows surgery

(Folkman effect).

Also, it correlates better with the modest benefit following the adjuvant sistemic

therapy.

This model emphasizes the fundamental importance of tumoral angiogenesis. It is known

that the solid tumors cannot develop more than 10 6 or aprox. ½ mm diameter, in the absence of

blood. The initial prevascular phase of development is followed by a vascular phase in which the

angiogenesis induced by the tumor represents a limitation of the rate of growth and insures the

malignant cells with direct access to circulation.(9)

Along the importance of microvascularization, is important to visualize these

microscopic focci into a citokine , endocrine polipeptids and steroids ‘soup’,with cells which
interract among them and with the surrounding stroma, interpreting the signals in competition

which direct the cancer cells either towards proliferation, or towards apoptosis.

The most important consequences of these theories were that the extension of local

treatment won’t lead to an improvement of survival and that the sistemical treatment is

necessary.

II. THE ROLE OF SURGERY IN DEVELOPMENT OF CONSERVATIVE

TREATMENT

1. The results of radical mastectomy techniques

Conservative surgery for breast cancer started 40 years ago, as alternative to mutilating

surgery, as Halsted or even super/radical mastectomies, followed by severe functional sequelae,

and sometimes not the best long term results .

Studying the results of radical and ultra/radical surgery in breast cancer it showed that

there are no significant improvements towards survival, despite local control, death coming

through development of distant metastases. This argument represents one of the most serious

argument which determined the raise of conservative treatment, aspect which correlates with the

importance given towards the quality of life.(7)

2. “Quality of life” concept

In the last years, the west countries gives a special importance to the quality of life and

consists of continuous preoccupation for insuring În an optimal confort in the patient’s life/

important aspect which is taken into consideration when the therapeutical strategy is decided.

3. The impact of randomized clinical studies

For most of the organs, the acceptance of a conservatory therapy necessitated only the

proof of feasibility and efficiency but not the equivalency with an alternative radical surgical

technique. On the contrary, the acceptance of conservatory surgical treatment in breast cancer as

a standard in practical oncology was possible only after finalizing of numerous randomized
prospective studies which demonstrated the equivalence with the mastectomy regarding the

control of the disease and the survival.

The first randomized controlled clinical study was made in London in 1972 by Atkins,

Haywards and col., and compared the Halsted mastectomy followed by regional lymph node

radiotherapy, with a therapy consisted of wide breast resection followed by breast radiotherapy

and on supraclavicular and internal thoracic lymph nodes , the results regarding the relapse and

long term survival pleads for mastectomy. These results lead to another multicentric international

study named Milano I, which compared Halsted mastectomy with what was called QUART

(quadrantectomy followed by radiotherapy with high energy of 50 Gy and overdose of 10 Gy on

the tumoral zone, without the regional lymph node radiation but with a wide

lymphadenectomy. ); were admitted in the study patients with infiltrated carcinoma smaller than

2 cm, without axillary nodes suspicion of metastatic invasion. The analysis published in 1980

demonstrated the best results on long term survival.

The second study called Milano II in 1985-1987 made a comparative analysis of 360

patients treated on QUART with 345 patients treated on TART (tumorectomy with

lymphadenectomy and radiotherapy of 45 Gy on the external tumoral bed followed by 15 Gy

intermediary application of Ir 192)

The long term survival is consitant with the other 2 groups, the little differences

regarding the local relapses not affecting the value of TART method.

The third trial , Milano III, made on tumors smaller than 2.5 cm, N0 or N1, published in

1997, after 95 months of follow up, compared the long term survival of 294 patients treated

according to QUART protocol with patients treated only by quadrantectmy and

lymphadenectomy. The results published by Veronessi, which also promoted the idea of

Veronessi technique, showed the same survival rates on long term.(12)

The EORTC study in 1980-1985 which compared 903 pacients with breast cancer in

stages I and II, with tumor smaller than 5 cm, divided into a group which received modified
radical mastectomy and another which received wide tumoral excision with lymphadenectomy

and radiotherapy, with administration of chemotherapy to all patients with positive axilary lymph

nodes showed the superiority of conservative surgery.

As a conclusion all these prospective studies on an important number of patients with 20

years follow up demonstrated that the conservatory treatment consisted of lumpectomy or

qudrantectomy plus axillary lymph node removal plus breast postoperative radiotherapy, applied

in stages I and II and showed similar results regarding global survival and disease free interval as

compared with radical mastectomy.(3)

Correaliting all these concrete studies regarding long term survival with the constant

preoccupation for quality of life insured to the patients diagnosed with breast cancer, it is obviuos

that the conservatory surgeyr imposed itself, if not everywhere as yet, in the treatment of breast

cancer, all direction of research converging now towards the improvement of these conservative

techniques. In the sense we can mention the development of sentinell lymph node concept which

lead to minimalization of surgical intervention amplitude, very important aspect because axxilary

lymphadenectomy is very aggressive and is followed by notable sides effects, being an essential

step which allowed the consolidation of conservative surgery.

III. SCREENING PROGRAMS

One of the fundamental problems of surgical conservative interventions in breast cancer

is representing by eligibility of conditions which allow the application of these surgery, out of

which the msot important one is the establishment of a more precocious stage.

Introducing the mammographic screening on a large scale was one of the most important

factors which created the precocious detection of breast cancer in initial stages in favor of

conservative surgery.(1)
 On international scale was establish a consensus based on clinical trials on long term, in

which the screening of breast cancer , made by clinical examination and mammography can

reduce the mortality of this disease till 50 %.

THE INDICATION OF CONSERVATIVE SURGICAL TREATMENT

The first problem which appears is establishing exactly the indications of conservative

surgical treatment.

Numerous studies tried to identify risk factors or prognostic factors for breast cancer

treated conservatively so that it can be formulated few criteria of selection for patients who can

benefit of this treatment.

The following circumstances are considered basic criteria which allow the application of

conservative surgical treatment:

- single tumors smaller than 2.5 cm

- absence of axillary lymph nodes with clinical characters of malignancy

- slow evolution of tumor in time

- express wish of the patient to save the breast.

- Remaining margins negative after resection by histo-pathologic examination

- Convenient tumor/breast ratio.

The most important are the ratio of tumor/breast and the possibility of insuring negative

remaining margins. (2)

Absolute contraindications of surgical conservative tratament:

- first and second trimester of pregnancy

- 2 or more voluminous tumors in separate quadrants of the breast

- imprecise diffuse microcalcifications or with malignant character

- pre-radiation of the breast

- cholagen disease.

Relative contraindications:
 - tumor/breast ratio leading to a poor cosmetical result

- voluminous breasts

- central quadrant localization of the tumor

Presently there is a tendency of modification of strategy of conservative surgical

treatment, because it is important to establish a therapeutical conduct in identifying especially

the contraindications more than indications. The contraindications are of two categories: the first

include the conditions which make impossible the control of local disease and the second one

which is represented by the contraindications of applying radiotherapy postoperatively.(8)

These are in fact the actual tendency of evolution of conservative surgical treatment,

which along with the efficiency of neo-adjuvant treatment, allows the extension of indications

also for advanced stages.

MATERIAL AND METHOD

THE EXPERIENCE OF SURGERY CLINIC II

Although this problematic represents a constant preoccupation in our Clinic, the number

of conservative surgical interventions are just a percentage of 8.14 out of the total number of

breast cancer surgeries.

In the period 2000-2005 in the Emergency Clinical Hospital of Constanta, in Surgery

Clinic II, 35 conservative interventions were done out of a total of 430 surgical interventions for

breast cancer.

RESULTS

Table I – distribution over years in the study cases

Graph no. 1A - distribution over years in the study cases

Graph no. 1B - distribution over years in the study cases

 The distribution according to age is represented in the table and the graph below, where it

is observed that a third of the cases are in between the interval 41-50 years of age.

Table no. II - distribution according to age

Graph nr. 2 - distribution according to age

The distribution of the cases according to TNM stages, which was done preoperatively,

is represented in the lower table, where it is shown the majority of cases in stage II- 40%

Table no. III - TNM stages

Graph no. 3 TNM stages

The types of surgical interventions that were used are presented in the following table.

Studying these data, the most frequent surgical intervention was sectorectomy (42.85%), ,

followed by immediate quadrantectomy ( 40%). In all cases axillary lymphadenectomy was done,

and postoperatively the patients were evaluated by the oncologist , who recommended in all

cases, radiotherapy, and the chemotherapy and the hormonotherapy depending on the axillary

lymph nodes demonstrated histopathologically and the biologic status.

Table no. IV - surgical technique variants

Graph no. 4 - surgical technique variants

DISCUSSIONS

THE DIAGNOSTIC PROBLEMS OF CONSERVATIVE TREATMENT

FOR BREAST CANCER IN OUR COUNTRY

Applying into practice the concept of conservative treatment involves solving problems

concerning the following:

- the necessity of screening program

- strict periodical control in the context of complex treatment.

 - Insuring technical techniques

- Forming and efficiency of senological teams.

 Medical education of the population

Medical education of the population represents a major problem not only for the

conservative treatment in breast cancer where the patients are a integrative part in the

therapeutical algorhythm , with a very important role in insuring its success, because it is

absolutely necessary that the patient understands the principles of conservative treatment, and

close collaboration with the doctor, but also for the whole society.(11)

From a different point of view, the success of screening program or the efficiency of

periodical control have on its base the good medical education of the population.

 The necessity of screening program

In the economical context of our country it is hard to predict when it is going to be

possible the implementation of screening program in breast cancer.

Still, for the three procedures of precocious identification in the screening of breast

cancer, the self examination of the breast, clinical examination by the specialized personnel and

the mammography - the efforts for obtaining the maximum efficiency in applying each method

must be identified even if the principles of a screening program are not totally followed.

Thus, self examination must be done in a systematic and instructed manner. It is a simple,

cheap, noninvasive method of identifying breast cancer and accepted by the older persons.

The instruction regarding self examination will be done explaining to women that it is

not a method of identifying cancer but the possibility of eventual modifications on breasts. In

fact, the ones in charge with presenting self examination start by defining it as a systematic

method done for identifying an anomaly.

 The doctors must be convinced of their role in education of the population regarding the

necessity of self examination technique and putting into practice.

The women who learn the practice of it form a doctor and medical personnel apply it

better than the ones who learn about it from other sources. Still the importance of information

through other means remains a reality.

The education of the population must be permanently done because nowadays there is a

tendency of abandoning the method.

Clinical examination has an important role in breast cancer because of its efficacy and its

simplicity, this exam being more eligible for medical personnel.

Today is indicated that starting with the age of 35 all women must take this examination

annually. This recommendation becomes indispensable to women who have one or more risk

factors and can be performed to all women who are getting a medical consultation in different

circumstances.

The mammography , the most important screening method of breast cancer, and the only

one which proved its contribution to the reducing of mortality, represents a neuralgic point of

these programs in our country, because of lack of technical instruments corresponding to the

amplitude of a screening national program.

 Strict periodical control in the context of complex treatment

Periodical control of diagnosed and treated patients, radically or conservative for breast

cancer, represents an important component of the strategy in the multimodal complex treatment

of breast cancer.

After applying the therapeutical sequences which correspond to primary treatment in

breast cancer, the patients need a careful surveillance oriented in two directions

One direction consists of precocious identification of malignant cell proliferation, which

can represent a local relapse to the level of ipsilateral breast after conservative surgery or the

appearance of cancer to the contralateral breast.

 The other direction has the purpose of monitorizing adverse effects of the treatments,

especially of the adjuvant one.

Making allowance of the importance of periodical control, the rigurousity of it

represents a compulsory condition which is included in the strategy of conservative treatment for

breast cancer.

 Insuring technical techniques

Conservative treatment for breast cancer represents a recent acquisition which implies

also insuring the technical means for application of this concept, such as imagistical evaluation

of the breast by MRI, using mini-invasive methods for precocious identification of breast cancer,

immunohistochemical analyses or identification of sentinel lymph node with gamma radiation

probe.(10)

 Forming and efficiency of senological teams

All these are necessary for inclining the therapeutical balance in favor of conservative

techniques, so that this therapeutical option to become a reality of breast cancer surgery in our

country.

FINAL CONCLUSION

The conservative surgery of the breast must become the election treatment of breast

cancer in stages I and II.

 SELECTIVE BIBLIOGRAPHY

1. BLIDARU AL, MIHAELA SEBENI, C. BORDEA, C. VIIŞOREANU, I.

BĂLĂNESCU: -Atitudinea faţă de leziunile mamare infraclinice descoperite mamografic,

Chirurgia (Buc.) 2000, 2, 95:109-117

2. BURCOŞ T. şi colab. – Locul chirurgiei conservatoare în cadrul

tratamentului oncologic complex al cancerului de sân, Chirurgia, 2003, 98(2)

3. FISHER B. - Reanalysis and results after 12 years of follow-up în a

randomized clinical trial comparing total mastectomy with lumpectomy with or without

irradiation în the treatment of breast cancer. NEJM, 1995, 333

4. FISHER B. (NSABP study - protocol B06) -Twenty Year follow-up of a

randomized trial comparing total mastectomy, lumpectomy and lumpectomy plus irradiation for

the treatment of invasive breast cancer. NEJM, 2002 347(16):1233 - 1241

5. GREENALL M.J. - Cancer of the breast. în “Oxford Textbook of Surgery”

on CD-ROM. Oxford University Press, 1995

6. HARRIS JR, LIPPMAN ME, MORROW M, OSBORNE CK. Diseases of

the Breast Second edition, Lippincott Williams & Wilkins, 2000.

7. JACOBSON A.J. - Ten year results of a comparison of conservation with

mastectomy în the treatment of stage I and II breast cancer. NEJM, 1995, 332 (14):907-911

8. MOGOŞ D. şi colab. – Chirurgia conservatoare a sânului – 7 ani de

experienţă, Chirurgia, 2003, 98(3)

9. PELTECU GH., sub redacţie – Tratamentul conservator al cancerului

mamar incipient, Ed. Universitară „Carol Davila” Bucureşti, 2003

10. PINOTTI JA, CARVALHO FM: Intraoperative monitorization of surgical

margins: a method to reduce recurrences after conservative treatment for breast cancer, Eur J

Gynaecol oncol 2001; 23 (1): 11-6

11. UNC O.― Valoarea tratamentului complex în cancerul de sân, Iaşi 1999,

Lucrare de Doctorat.

12. VERONESI U. - Twenty Year follow-up of a randomized study comparing

breast - conserving surgery with radical mastectomy for early breast cancer. NEJM, 2002, 347

(16):1227 – 1232
Table I – distribution over years in the study cases

year 2000 2001 2002 2003 2004 2005 Total

Breast cancer 66 68 61 81 80 74 430

Conservative surgery 4 6 5 7 8 5 35

percentage 6.06 8.82 8.19 8.64 10 6.75 8.14

90

80

70

60

50

40

30

20

10

0
2000 2001 2002 2003 2004 2005

total no. of interventions conservative interventions

Graph no. 1A - distribution over years in the study cases

10 10
9 8.82 8.64
8 8.19
7 6.75
6 6.06
5
4
3
2
1
0
2000 2001 2002 2003 2004 2005

Graph no. 1B - distribution over years in the study cases

Table no. II - distribution according to age

age No. of cases %

<20 0 0
21-30 0 0
31-40 4 11.42
41-50 12 34.28
51-60 9 25.71
61-70 8 22.85
>70 2 5.71
 5.71 11.42

22.85 31-40
41-50
51-60
61-70
34.28 >70

25.71

Graph nr. 2 - distribution according to age

Table no. III - TNM stages

Stages Number of cases %

0 4 11.42

I 12 34.28

II 14 40

III 5 14.28
 11.42
14.28

0
I
34.28 II
III
40

Graph no. 3 - TNM stages

Table no. IV - surgical technique variants

Surgical intervention No. cases %

Sectorectomy 15 42.85

Quadranectomy 14 40

Duble quadranectomy 5 14.28

Triple quadranectomy 1 2.85

 2.85
14.28
Sectorectomy

Quadranectomy
42.85
Duble
quadranectomy
Tripla
40 quadranectomy

Graph no. 4 - surgical technique variants